Autosomal polycystic kidney disease is the most common inherited kidney disease determining 5% of all end-stage kidney disease. The only therapy approved for this condition is Tolvaptan, which, with its aquaretic effect, has a strong effect on patients’ daily life. Recently, the literature has been enriched with new works that analyze possible non-pharmacological therapeutic strategies to slow cysts’ enlargement and chronic kidney disease progression. Among them, dietary schemes reducing carbohydrate intake and inducing ketoses have been demonstrated to have efficacy in several pre-clinical and clinical studies. A ketogenic diet, calorie restriction, intermittent fasting, and time-restricted feeding can reduce aerobic glycolysis and inhibit the mTOR pathway, producing a reduction in cyst cell proliferation, a reduction in kidney volume, and helping to preserve kidney function. ADPKD’s burden of disease has an impact on patients’ quality of life, and the possibility to play sports or carry out physical exercise can help people in everyday life. The multisystemic character of the disease, especially cardiovascular involvement, needs to be carefully evaluated to establish the quality and quantity of physical activity that patients can safely carry out. Autosomal polycystic kidney disease (ADPKD) is the most common inherited kidney disease and is characterized by a gradual and slow formation and growth of kidney cysts leading to end-stage kidney disease. In recent years, the lifespan of polycystic patients has increased thanks to several strategies that have improved the symptoms and complications of the disease. Tolvaptan is the only drug approved for ADPKD treatment and it has been demonstrated to be effective in the reduction of cyst growth, but its aquaretic effect may change patients’ daily living habits.An Increasing number of studies report important association between diet, physical activity (PA), and health-related quality of life (QoL) both in the general population and in several pathological contexts, such as in oncological patients ,2,3. At Some studies have recently evaluated the impact of diet on the disease and have also hypothesized the use of dietary strategies for the treatment of the disease. The purpose of this review is to describe the specific domains of diet and physical activity for polycystic disease, laying the basis for a complete overview of these areas which widely influence the life of polycystic patients, and which must be taken into strong consideration during their multispecialty management.The incidence of ADPKD is about 1/400–1/1000 born alive .Mutations in two genes, PKD1 (chromosome 16p13.3) and PKD2 (chromosome 4q21), are responsible for the disease, in particular, changes in PKD1 are attributable to 85% of cases while most of the remaining cases (10%) come from alterations in PKD2 . NeverthPKD1 and PKD2 encode two integral membrane proteins associated with the primary cilia called polycystin 1 (PC1) and polycystin 2 (PC2), respectively. PC1 has a role in cell–cell interaction and matrix–cell interaction, it has a receptor function, modulating the opening of voltage-dependent calcium channels and potassium channels. PC2 is instead a voltage-dependent calcium channel . The intStudies have shown that the flexion of the primary cilia produced by kidney flow is transduced through changes in intracellular calcium concentration . AccordiThe role of cAMP (cyclic adenosine monophosphate) is crucial; mutations in PKD1 and PKD2 lead to a reduction in intracellular calcium and an increase in cAMP. This activates protein kinase A (PKA) and increases the sensitivity of the principal cells of the collector duct to the constant stimulus of vasopressin (AVP); it promotes altered tubulogenesis, cell proliferation, increased secretion of fluids, and interstitial inflammation . AVP alsCurrently, Tolvaptan, a highly selective antagonist at the V2 vasopressin receptor (AVP), is a specific therapy approved for the treatment of ADPKD; it has been demonstrated that Tolvaptan reduces the growth rate of cysts and slows the increase in TKV, slowing ESKD. As described earlier, AVP binding with its V2 receptors stimulates cAMP production in the distal nephron and collector duct inducing cyst growth. The effects achieved by blocking AVP action through an antagonist are aquaresis, reduction in urinary osmolarity, and reduction in cyst proliferation mediated by the suppression of cAMP production ,12.Dietary interventions are a fundamental part of chronic kidney disease (CKD) treatment, demonstrated by their impact on slowing the progression of CKD and reducing the accumulation of metabolic products, helping in lowering symptoms of uremia and metabolic acidosis and lowering phosphate levels.Among the dietary regimens, plant-based diets and dietary approaches to stop hypertension (DASH) may be beneficial in slowing CKD progression with their low sodium, saturated fat, phosphate apport, and high fiber intake. In addition, plant-based regimens are alkaline-forming, helping in the reduction of acidosis condition in advanced chronic kidney disease ,14,15,16Similarly, the Mediterranean diet is advantageous in slowing kidney damage progression and cardiovascular disease thanks to the reduction in oxidative stress .However, to the best of our knowledge, there are no studies published in the literature that analyze the efficacy of these regimens in reducing cyst formation and growth in ADPKD patients, even if it could be an interesting field to examine because of the possible high adherence to this diet.In ADPKD patients, nutrition must be appropriate to the management of CKD, aiming to limit its complications and the progression toward end-stage kidney disease, while maintaining a good nutritional status . MoreoveMost of the nutritional suggestions for the management of CKD in ADPKD derive from the general recommendations for CKD due to different etiology in particular.Proper protein intake can help prevent or improve part of the metabolic imbalances due to chronic kidney disease. Prescription of a low-protein dietary regime remains one of the most widely used strategies for the management of symptoms related to uremic toxicity in CKD patients. The amount of protein is defined by the CKD stage:  stages 1Protein restriction has been proven to delay evolution to ESKD in non-ADPKD CKD patients, as shown in the Modification of Diet in Renal Disease (MDRD) study  where itThe CRISP study initially showed an association between total kidney function increase and GFR decline and protein intake; however this association was not confirmed after adjustment for important confounders .An elegant work conducted by Heida et al. showed a strong association between a high urine-to-plasma urea ratio and GFR decline in polycystic adult patients. Considering that the urine-to-plasma urea ratio positively correlates with protein intake, such a result suggests how low protein consumption could slow the worsening of kidney function even in ADPKD patients .However, the majority of experts suggest the avoidance of very low protein intake (<0.6 g/kg/die) for malnutrition risk and suggest that if a similar regimen is adopted there be strict and careful monitoring of patients with trimestral or at least semestral follow-up .Due to the lack of strong evidence, there is not a widely accepted guideline on protein intake in ADPKD patients and neither does the KDIGO Controversies Conference on ADPKD specify a protein regime . The KDOThe importance of lowering salt intake is a priority in CKD patients. The aim is to keep sodium intake lower, to 90 mmol/day, corresponding to the consumption of less than 2000 mg/day of sodium (Na) and <5 g/day of sodium chloride (NaCl). This leads to better management of blood pressure, limitation of kidney damage, and a better cardiovascular outcome .Phosphate homeostasis abnormalities are frequently observed in patients with reduced kidney function and are often predictive of negative clinical outcomes. Hyperphosphatemia contributes to the burden of cardiovascular disease leading to cardiovascular and soft-tissue calcifications, cardiac disease, renal osteodystrophy, and secondary hyperparathyroidism. Phosphorus requirements depend on the stage of CKD and should consider the avoidance of malnutrition, not unusual in ESKD and dialysis patients .Kidney’s potassium excretion is reduced with the lowering of the glomerular filtration rate, and hyperkalemia is a severe condition commonly experienced by CKD patients. Monitoring of potassium serum levels is fundamental, and the target values are 3.5–5.0 mmol/L to be reached with lower potassium diets and, if necessary, with hypokalemic drugs .High protein intake is associated with hyperfiltration secondary to the secretion of glucagon, strictly associated with gluconeogenesis in the liver and with urea excretion by the kidneys, together with cAMP released from the liver. A protein-rich meal induces simultaneous vasopressin release improving urine concentrating ability, as shown in some studies on healthy humans in which GFR after high protein intake significantly correlates with increasing urine osmolality. The two hormonal pathways lead to increased urea excretion and water reabsorption, reducing the tubuloglomerular feedback (TGF) signal at macula densa and then increasing GFR, inducing hyperfiltration . This meIndeed, in a study on DBA/2FG-pcy (pcy) mice, Aukema et al. showed how a low protein regimen has a positive impact in reducing cyst growth and kidney volume in comparison with a normal protein diet . The samVasopressin (AVP) stimulates cyst growth in ADPKD. Increased water intake is recommended for AVP secretion suppression, which reduces AMPc synthesis and consequently cyst growth  and imprThe DRINK study explored a high-water intake regimen in humans as an alternative to pharmacological therapy in blocking vasopressin. The patients were divided into two groups: high water intake (HW) and ad libitum intake (AW); the 8-week experiment showed that the osmolarity target (<270 mOsm/kg) could be reached by the majority of the patients in the HW intake group without difficulty, demonstrating the feasibility, safety, and adherence to a possible water therapy .Another study published by Rangan et al. in 2022 studied two groups of ADPKD patients, one with high water intake versus one with ad libitum intake, and even though a reduction in urinary osmolarity was observed in the high-intake group, no differences in kidney volume emerged .What is important to underline is the necessity of further trials to verify the effects of water intake on the progression of ADPKD.Otherwise, increased water intake has also been shown to counteract nephrolithiasis, reducing the risk of stone formation, one of the main comorbidities of ADPKD .Sodium restriction in ADPKD may be favorable because of the reduction in renin angiotensin aldosterone system activity. Aldosterone induces the transcription of the alpha subunit of Na/K ATPase which may promote, in ADPKD patients, fluid secretion and cyst enlargement. In addition, through the epidermal growth factor receptor, it stimulates kidney fibroblast proliferation and the proliferation of dedifferentiated kidney tubule cells .Additionally, blood pressure control has been demonstrated to be fundamental in disease progression. As with the other causes of CKD, even in ADPKD patients, strict management leads to a slower reduction in GFR and a lower annual increase in kidney volume .p = 0.02), and urinary osmolarity decreased from 426 ± 193 to 258 ± 117 mosm/kg (p = 0.01), while they remained unchanged in the control group. Thus, suppression of AVP is also possible by managing sodium intake and without large increases in water intake, which may be more difficult to maintain in the long term.T restriction also reduces vasopressin levels. Amro et al.  performeFurthermore, in Hane:SPRD mice (a model for polycystic kidney disease), an increase in sodium intake is accompanied by a higher kidney weight and cyst dimension . 2/year for each gram of salt reduction) and also with a lower incidence of composite renal endpoint  [However, the literature on randomized trials investigating the effect of a reduction in salt intake in the progression of ADPKD disease is scarce. The best evidence available is from a post hoc analysis of the HALT A and B trials where the effect of blood pressure control and RAAS blockade was investigated in ADPKD. In particular, the post hoc analysis showed that a decrease of 1 g in salt intake is associated with a reduction in kidney growth (0.43%/year) and GFR decline (−0.09 mL/min/1.73 mr death) . In concHigh phosphate levels in ADPKD could induce tubular injury, promoting cyst growth and disease progression.Omede et al. suggested that restriction in the dietary intake of phosphates may be able to slow cystic development and fibrosis in PKD. To verify this, the authors divided the PKD mice into two identical groups and fed them with two regimes differing only in phosphate intake (normo-phosphoric and hypo-phosphoric). Dietary phosphate restriction resulted in a 25% lower kidney weight/body weight ratio, a reduction in the number of cysts, and expression of tubular injury markers  .Caffeine is a methylxanthine that increases the levels of intracellular cAMP in cultured renal ADPKD epithelial cells. A retrospective analysis of the CRISP study cohort found no association between caffeine consumption and a higher increase in hTKV , progression to ESKD, or death in 239 patients with an average follow-up of 12.5 years . Even daAppropriate nutrients and calorie intake must always be reached in order to avoid malnutrition and related complications . Caloricp < 0.001) after a follow-up of five years. This could be due to continuous caloric excess, leading to strong activation of the mTOR pathway with relative suppression of AMPK (adenosine monophosphate-activated protein kinase), leading to the proliferation of cysts. Following this hypothesis, it has been thought that slight/moderate calorie restriction, activating AMPK and suppressing mTOR, could slow the progression of the disease [There are currently few studies concerning the association between overweight/obesity and the decline of kidney function in ADPKD. Nowak et al. investigated this correlation by analyzing data from 441 non-diabetic participants in the HALT PKD study A with early ADPKD . The sub disease  showed h disease  investigThe beneficial effects of food restriction in several aspects of health appears to be related to the insulin growth factor-1 (IGF-1) pathway, which is also dysregulated in cancer and aging. In ADPKD, IGF-1 could be involved in cyst proliferation; in fact, some studies have found increased expression of IGF-1 in polycystic patients and animal models . The worIn addition to the classic diet approach, interesting new strategies are being increasingly studied, such as calorie restriction or diets inducing ketosis states.A KD is carried out with careful food planning, with macronutrients in predetermined proportions. The classic approach is based on the lipid ratio which can vary from a four parts fat (long-chain triglycerides) to a one-part combined protein and carbohydrate ratio (from 4:1 to 2:1), supplemented with minerals and vitamins .Nowadays, in addition to the classic KD mentioned above, there are new approaches able to induce a ketogenic status, more tolerated in the long-term, such as the modified Atkins diet, the MCT diet, or versions of intermittent fasting (for example time-restricted feeding), which are commonly used in daily practice.Recent studies ,50,51,52The rationale behind using a KD approach in ADPKD patients has been explored by several works ,53,54,55The positive effects of ketosis appear to be, at least in part, due to the increase in BHB, since this would be able to independently modulate the pathways of mTOR and AMPK. In fact, it has been demonstrated in animal models that using oral supplements containing BHB simulates the effects of ketosis induced by diet . Torres 2. The participants with documented ketosis showed the highest augmentation of eGFR, with an increase of 7.3 mL/min/1.73 m2. However, it is important to point out that the improvement in kidney function should be analyzed deeper with other techniques that are more accurate, such as creatinine clearance or kidney scintigraphy to define if it is real or is due to hyperfiltration or malnourishment which are not a desirable effect of the ketogenic regime. The principal side effects of the diet were fatigue, reported by 66% of participants, hunger, and the typical symptoms of keto-flu , symptoms that in almost all patients disappeared after a short time after adaptation to ketosis. Ultimately, most of the participants considered KD and TRF feasible; however, they reported a higher difficulty in long-term maintenance especially in the DK regimen. These results are promising, nevertheless, all data are reported by the patients themselves, obtained in an uncontrolled environment and without balance between men and women; thus, the reliability is very limited, with a strong bias, but this experience may be useful for future clinical trials.Moving from animal models to human evidence, Strubl et al. published a retrospective study in which they collected through questionnaires the experience of ADPKD patients who had already carried out ketogenic diets and TRDs (restricted-time diets) in the past in order to obtain information on the safety, feasibility and possible benefits of this regimen on the PKD patient . From th2). As mentioned before, even this work has the limitation of evaluating kidney function with the measure of creatinine and estimation of the glomerular filtration rate.The potential benefits of ketosis in ADPKD have recently been discovered and for this reason, there are very few clinical trials published or in progress concerning the ketogenic regimen in humans ,59,60 anA study by Testa et al. tested the feasibility and potential benefits of a modified Atkins diet in ADPKD patients . The choAnother interesting study, the first prospective interventional trial, RESET-PKD , confirmNew randomized controlled clinical trials are currently ongoing and are evaluating time-restricted feeding , caloriePhysical exercise in ADPKD patients has limited published data. In general, it is known how fundamental physical activity (PA) is in maintaining and improving cardiovascular and metabolic fitness, and the importance of controlling these factors in CKD is also known. It is reasonable to think that such benefits could also apply to ADPKD patients, where the burden of cardiovascular disease is often particularly significant.The KDIGO 2021 guidelines recommend that all patients with kidney disease must be involved in at least 150 min of PA per week. The form and intensity of exercise should be constructed on an individual basis, as there may be health benefits even when levels of exercise are lower than recommended . PhysicaThe condition of ADPKD requires some specific precautions in prescribing physical activity. In a healthy subject, physical exercise determines an increase in heart rate and output with simultaneous dilation of the peripheral vascular bed and a subsequent reduction in resistance; the increase in output raises systolic pressure, while diastolic pressure remains unchanged or decreases through peripheral vasodilation . SeveralMartinez-Vea et al. studied young ADPKD patients after physical exercise to assess their cardiovascular response and they found echocardiographic signs of early diastolic dysfunction with an exalted response of systolic pressure and little decrease in diastolic pressure secondary to reduced vasodilating capacity . AnotherReinecke et al. evaluated the response to exercise in polycystic adults with no evidence of ventricular hypertrophy and with normal kidney function. The test consisted of 20 min of use of an exercise bike and bio-humoral measurement; the results were a reduced anaerobic threshold and reduced maximum oxygen consumption, with a low response of NO (nitric oxide) and ADMA (asymmetric dimethylarginine) during acute exercise. These are all indicators of the possible presence of early endothelial dysfunction in this pathology while there was no correlation between this type of cardiovascular abnormalities and TKV .In conclusion, there is no doubt that patients affected by ADPKD, like other nephropathic patients, must perform regular exercise according to indications of KDIGO 2021 but with special precautions. For example, contact sports such as rugby, boxing, and football should be avoided in order to prevent abdominal trauma which could cause cysts to rupture and subsequent bleeding. Considering the cardiovascular profile previously described, it is recommended to carry out a complete cardiological screening before starting sports and exercises.From the literature, it has emerged that the current nutritional approach towards patients with ADPKD is derived from that elaborated for CKD due to other causes. However, there are fundamental differences due to the peculiarities of the disease and the necessity to slow the growth of cysts.For this reason, as the literature has demonstrated, it is fundamental to maintain a normal weight with a BMI between 18.5 and 24.9, since an overweight/obesity condition has been identified as a significant driver of cyst growth , resultiAs precautionary measures, moderate coffee consumption and higher water intake are suggested, as this, in the same way as the decreased intake of salt/sodium may act, could decrease urinary osmolarity and, consequently, inhibition of AVP resulting in the suppression of cAMP .Interesting prospects of nutritional treatment have been explored through the adoption of specific diets, such as calorie restriction, classical intermittent fasting, and some of its variants such as time-restricted feeding. The reason for studying these regimens is based on the inhibiting effect of calorie restriction on the mTOR pathway, which is constantly active in ADPKD patients leading to the inhibition of AMPK and stimulating cell proliferation and cystic development. As a result of the restriction, the ATP/AMP ratio decreases and AMPK is activated, resulting in mTOR inhibition. In experiments on animal models of PKD , it has There is increasing interest in the ketogenic approach, analyzed in several animal model experiments. The rationale behind the use of this regime comes from the discovery of the metabolic inflexibility of cyst cells and their “Warburg-like” metabolism. Even the induction of a state of ketosis determines a state of nutrient deficiency that activates the inhibition pattern of mTOR. Moreover, the increase in circulating fatty acids leads to higher lipids uptake by the cyst cells, leading them to die from lipotoxicity. Another actor in this process seems to be BHB, the ketone body mainly produced in ketosis, which alone would modulate the pathway of mTOR and AMPK. In support of the ketogenic approach and integration with BHB, Torres et al. in a recent study hypothesized that the benefits seen with various intermittent fasting regimens are not due to kcal restriction by itself but are to be attributed to the partial ketosis induced by fasting itself, resulting in an increase in circulating ketone bodies, in particular BHB ,55.It is important to note that the majority of studies that analyze nutritional treatment on humans affected by ADPKD have the limitation of being observational studies, on small populations, and some of them have patient-reported measurements. Considering the impact of dietary regimens on the progression of the disease, it is desirable that a new randomized controlled trial would be developed to increase knowledge in this field.As recommended by the KDIGO 2021 guidelines, in CKD conditions, the maintenance of at least 150 min of physical activity per week has been shown to have positive effects on overall health, counteracting functional decay and thereby reducing the risk of mortality . In addiIn view of the great benefits to physical and mental health derived from physical activity, there is no doubt that people with ADPKD should lead an active lifestyle but with particular attention. For example, contact sports such as rugby, boxing, football, and others should not be practiced to prevent abdominal trauma from causing cyst rupture, resulting in bleeding and pain . In addiThe results from research underline the importance of a multidisciplinary approach to ADPKD patients in order to provide the best follow-up for patients with a disease that determines renal but also extrarenal manifestation.Further studies are needed to increase the evidence currently present on the effect of diet and physical activity in polycystic patients and to understand which nutritional and behavioral strategies can best support current pharmacological strategies for slowing down kidney damage in ADPKD.


Low density of formal care providers in rural India results in restricted and delayed access to standardized management of hypertension. Task-sharing with pharmacies, typically the first point of contact for rural populations, can bridge the gap in access to formal care and improve health outcomes. In this study, we implemented a hypertension care program involving task-sharing with twenty private pharmacies between November 2020 and April 2021 in two blocks of Bihar, India. Pharmacists conducted free hypertension screening, and a trained physician offered free consultations at the pharmacy. We calculated the number of subjects screened, initiated on treatment (enrolled) and the change in blood pressure using the data collected through the program application. Of the 3403 subjects screened at pharmacies, 1415 either reported having a history of hypertension or had elevated blood pressure during screening. Of these, 371 (26.22%) were enrolled in the program. Of these, 129 (34.8%) made at least one follow-up visit. For these subjects, the adjusted average difference in systolic and diastolic blood pressure between the screening and follow-up visits was −11.53  and −4.68  mmHg, respectively. The adjusted odds of blood pressure being under control in this group during follow-up visits compared to screening visit was 7.07 . Task-sharing with private pharmacies can lead to early detection and improved control of blood pressure in a resource-constrained setting. Additional strategies to increase patient screening and retention rates are needed to ensure sustained health benefits. About 55 million Indians are estimated to suffer from cardiovascular diseases (CVDs) causing an economic loss of $94 billion annually. India accounts for one-fifth of the global deaths due to CVDs . India’sRural India is estimated to have one allopathic doctor  for every 10,000 individuals –9  in the Bhojpur district of Bihar (India), Behea and Udwantnagar  . The phaFigure previously diagnosed. Subjects with no known history of hypertension were classified, based on their blood pressure reading, as either normotensive (systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg) or previously undiagnosed (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg). The previously undiagnosed and previously diagnosed groups were collectively classified as potentially hypertensive.Pharmacists screened adults visiting the pharmacy by measuring their blood pressure for free and stored the patients’ electronic health records in the program application after taking informed consent in the local language. Subjects with a self-reported history of hypertension were classified as A trained allopathic physician (GP) was recruited for the program duration. The GP visited each pharmacy based on a predetermined schedule at monthly intervals and offered free consultations to all individuals identified as potentially hypertensive on the first screening. The pharmacists informed potentially hypertensive subjects about the future visit date(s) of the GP at the pharmacy. Using the tablet device, the pharmacist could book a consultation for the subject with the project GP on a specific date and time. To ensure equitable access and incentivize screening, normotensive subjects were also provided free GP consultation but did not have the option to pre-book an appointment. During the consultation, the GP confirmed the diagnosis of the potentially hypertensive subjects and prescribed medication based on the standardized hypertension treatment protocol . The phaSubjects with confirmed diagnosis of hypertension (previously diagnosed and undiagnosed) were encouraged to enroll in the program for free follow-ups with the pharmacy and the GP. Previously diagnosed individuals had the option to enroll in the program without the project GP diagnosis as well. Enrolled subjects were encouraged to follow-up with the pharmacy monthly and record their blood pressure readings and refill medication if required. Additionally, subjects received follow-up reminder calls from the pharmacists to promote medication adherence and follow-up consultations during subsequent scheduled GP visits. At subsequent GP visits, patients received regular hypertension care.We used the programmatic data collected through the pre-installed application for our analysis. The demographic variables  and the self-reported diagnosis status of the subjects were collected at the first visit. The longitudinal data, recorded at every visit, included blood pressure measurements at each visit, an identifier to mark if each visit was a GP consultation or a pharmacy visit, and enrollment status of the subject. As part of the data cleaning, we identified records with missing blood pressure values. If an additional reading was available for the same calendar day and it was valid, that reading was used to replace the missing value. An individual could have multiple readings on the same day if the data was recorded by both pharmacist and doctor, or if either recorded the data twice. We removed records wherein either the SBP/DBP was not recorded or could not be restored, or a 0 value was recorded. We also removed records with unusually high values of SBP (>250 mmHg).All participating pharmacists were provided with an Omron HBP-1320 sphygmomanometer . PharmacThe pharmacists were trained on the blood pressure measurement protocol based on the guidelines followed by the IHCI . Blood pWe defined four operational outcomes of the program: (i) the number of subjects screened for hypertension during the program, (ii) the number of subjects who had at least one GP consultation, (iii) the number of subjects enrolled in the program, and (iv) the number of subjects who did a subsequent follow-up visit with either the pharmacist or the GP. The first outcome was disaggregated into three mutually exclusive categories based on their blood pressure at the time of screening and diagnosis history: previously diagnosed with hypertension, previously undiagnosed (no previous history of hypertension and had elevated blood pressure at screening), and normotensive .To analyze downstream health outcomes, we considered enrolled subjects with one or more follow-up visits. For each of them, we estimated the change in SBP and DBP and the odds of blood pressure being under control (SBP < 140 mmHg and DBP < 90 mmHg) during follow-up visit(s) compared to the screening visit. To estimate the change, we developed a linear regression model with the dependent variable as the SBP (or DBP) during each visit of the eligible subject. To estimate the odds of blood pressure being under control, we developed a logistic regression model with the binary dependent variable indicating if the subject’s blood pressure was uncontrolled (=0) or controlled (=1). The main explanatory variable of interest for these regression models was a categorical variable indicating if the observation was for the initial visit (=0) or a follow-up visit (=1). We estimated these models without (unadjusted) and with (adjusted) patient-fixed effects. The fixed effects controlled for observed  and unobserved fixed patient characteristics. In all models, we clustered the standard errors at the level of a pharmacy. We fitted additional models to assess if the effect of the follow-up visits differed by age, sex, and prior diagnosis of hypertension. The mathematical specifications of these regression models are available in the Supplementary Text.The operational outcomes were calculated using Python 3.8, and the regression models for the health outcomes were estimated using R 4.0.The baseline characteristics of the subjects screened in the program is tabulated in Table The program screened 3403 subjects for hypertension. Table Of the 3403 individuals screened, 1415 subjects were potentially hypertensive. These included 740 (52.3%) previously undiagnosed, and 675 (47.7%) previously diagnosed. Of the 675 previously diagnosed subjects, 440 (65%) had high blood pressure at the time of screening.p-value < 0.001). Of the 291 previously undiagnosed subjects who consulted with the GP, 225 (77%) were confirmed with a diagnosis of hypertension. Among the previously diagnosed subjects, 233 (71%) of the subjects were confirmed with diagnosis of hypertension out of the 328 patients who sought consultation.Among the 1415 potentially hypertensive subjects at screening, 619 (44%) subjects consulted with the GP. These included 291 (39%) of the 740 previously undiagnosed subjects and 328 (49%) of the 675 previously diagnosed subjects. This difference between the two groups was statistically significant  in proportion of patients with at least one follow-up between previously undiagnosed and previously diagnosed groups of patients.Of the 225 previously undiagnosed individuals with confirmed diagnosis, 86 (38%) enrolled in the program and 37 (43%) of these had at least one subsequent follow-up visit. Of the 233 previously diagnosed subjects with confirmed diagnosis from the project GP, 200 (85%) enrolled in the program. An additional 85 previously diagnosed subjects enrolled directly in the program without a GP consultation. Of these 285 previously diagnosed and enrolled subjects, 92 (33%) made at least one subsequent follow-up visit during the project period. There was no statistically significant difference (n = 129) after excluding one subject due to potentially incorrect blood pressure readings at follow-up. Baseline characteristics of this sub-sample of patients are in Supplementary Table To evaluate the clinical outcomes, we considered subjects with at least one follow-up visit n = 29 after Among enrolled individuals, assuming patients without a follow-up reading have uncontrolled blood pressure (a pessimistic scenario), the proportion of individuals with controlled BP reduced from 23.72% at time of screening to 11.05% at the end of the program. If we assume that patients without a follow-up reading maintain their blood pressure until end of the program, the proportion of individuals with controlled BP increase to 28.03% at the end of the program.n = 129). The proportion of subjects with controlled blood pressure increased from 13.5% at screening to 35.1% at the last follow-up for previously undiagnosed group and from 21.7% at screening to 30.4% at the last follow-up for previously diagnosed group. Taken together, the proportion rose from 19.2% at screening to 32.3% at the last follow-up among all individuals with one or more follow-up visits. .Figure The regression results for change in blood pressure with follow-up are tabulated in Table We did not observe any statistically significant differences in the outcomes  between previously undiagnosed and previously diagnosed subjects or between males and females. Older subjects had a greater reduction in SBP with follow-up but no statistical difference in change in DBP or odds of blood pressure control. The detailed regression results are provided in Supplementary Tables India’s rural population has restricted access to standardized hypertension care due to a severe shortage of formal care providers. Task-sharing is seen as possible means to bridge the gap. The Bihar Pharmacist Hypertension Study provides real-world evidence on the impact of task-sharing with pharmacists for hypertension screening and management. In particular, we find that such task-sharing leads to reduction in SBP and DBP and increased odds of controlling blood pressure for subjects enrolled in the program, who completed at least one follow up visit. However, it is noteworthy that only 35% of the enrolled hypertensive subjects followed for one or more visits over five months of the program. However, among those patients who did follow up, the proportion with controlled blood pressure at last follow up increased by over 12% after five months of the program.Our findings agree with those from previous studies on task-sharing of hypertension care with pharmacists. A meta-analysis of interventions in LMICs found that team-based hypertension treatment including task-sharing with pharmacists resulted in a change of –8 ∙ 12  mmHg in SBP and a change of −3.74  mmHg in DBP. A change of −5.8  mmHg in SBP and −7.1 (−9.8 to −4.2) mmHg in DBP was observed among 77 subjects (over six months) receiving pharmacy-led care in a diabetes clinic in Jordan , 19. A rDespite the promising impact on blood pressure, the long-term health outcomes from such a program rely on continued adherence to medication and follow-up with the care provider , 23. OnlHowever, due to the chronic nature of hypertension, financial incentives for treatment adherence might be unsustainable. A possible alternative to increasing patient retention may be creation of community support groups as observed in an intervention conducted in the slums of Nairobi, Kenya . Also, wPatient or pharmacist financial incentives may have improved follow-up in the Bihar Pharmacist Hypertension Study. Our program did not cover patient out-of-pocket expenditure for medication, travel, or wage loss (if any) during pharmacy or GP visits. It is likely that if the program covered such expenses, it would have improved patient retention. A modeling study conducted in India demonstrated that improving patient retention would have significant long-term health and economic benefits . SpecifiAny future scale-up of the program critically hinges on the sustained involvement of the pharmacists delivering the intervention, which also likely depends on the financial benefits accrued to them. The program did not remunerate the pharmacies based on the assumption that pharmacies would benefit from increased pharmaceutical sales due to the intervention and GP visits. However, it is possible that the pharmacies may not perceive the same benefit. Further, it is plausible that the pharmacy catchment area might have limited customers, and the pharmacies might run out of new customers after some time, which may diminish their interest in the program in the long term.The Bihar Pharmacist Hypertension Study was limited by not including a comparator group who were randomized to follow up in a traditional medical setting after screening. However, a comparator group was not included in the study design due to resource constraints. Geographic coverage was limited to two blocks in a single district of India; these results may not represent the feasibility of a community pharmacy model of hypertension care in other areas of India. However, the study’s setting was representative of large swathes of rural India suffering from poor public health infrastructure and lack of access to formal, standardized care. Our study design did not include data collection on out-of-pocket expenses of patients, and we did not model long-term health benefits. While a scale-up is likely to be beneficial, a future study on the cost-effectiveness analysis of a scaled-up task-sharing program can help compare the approach to other preventive programs. The participation in the program might have also been impacted as the study period partially overlapped with the second wave of the COVID19 pandemic in India (March–April 2021) . The redThe experiences and outcomes of the Bihar Pharmacist Hypertension Study provide policymakers with a plausible model for collaborating with the private sector to increase access to healthcare for chronic conditions like hypertension in areas with weak public healthcare delivery capacity. Although our program employed its own itinerant GP, other intervention designs could be tested. For example, the GP could supervise pharmacist care by way of telemedicine consultations, or pharmacists could screen patients but refer them to the nearest primary health center in the public health system for diagnosis and follow up care. Similar approach has yielded encouraging results in treating drug-resistant TB in India and identifying new TB cases . CommuniThe Bihar Pharmacist Hypertension study demonstrated the feasibility of team-based hypertension care involving community pharmacists in rural India. Hypertension outcomes were favorable among the one-third of enrolled patients who returned for follow up. However, to be successful, team-based care programs involving pharmacists must improve patient retention by focusing on aligning provider and patient incentives to improve quality in terms of patient screenings, enrollment, and retention.Task-sharing with non-physician healthcare workers can aid in the management of hypertension in resource-constrained settings.Rural India, while lacking formal care facilities, is catered by more than 800,000 private pharmacies.There are no known studies of task-sharing with private-sector pharmacies to aid the management of hypertension.Task-sharing with private sector pharmacies can lead to the early detection of hypertension, and lead to improved outcomes in the control of blood pressure in rural India.Managing patient retention and incentives for pharmacist participation is important for the success of a task-sharing initiative.Supplementary Appendix


The retinal nerve fibre layer (RNFL) was significantly lower in the outer nasal area  in ganglion cells and inner plexiform layers (GCL+) in DM2. A positive correlation between the LDL-C and RNFL and a negative correlation between HDL-C levels and the inner temporal and central RNFL thickness were detected. The central (p = 0.021) and inner nasal (p = 0.01) areas were negatively correlated between the RNFL and MAIA, while GCL++ was positively correlated with the outer inferior (p = 0.015) and outer nasal areas (p = 0.024). Retinal sensitivity and macular RNFL thickness decrease in DM2 patients with moderate DR with no DME, and this study enables an accurate approach to this disease with personalised assessment based on the DR course or stage. Thus, GCL+ and GCL++ thinning may support ganglion cell loss before the RNFL is affected.The increase in diabetic retinopathy (DR) prevalence demonstrates the need for the determination of biomarkers for assessing disease development to obtain an early diagnosis and stop its progression. We aimed to analyse total retinal (RT) and inner retinal layer (IRL) thicknesses in type 2 diabetes mellitus (DM2) patients and correlate these results with retinal sensitivity using swept-source OCT (SS-OCT) and microperimetry. For this purpose, a total of 54 DM2 subjects with moderate diabetic retinopathy (DR) with no signs of diabetic macular oedema (DME) and 73 age-matched healthy individuals were assessed using SS-OCT to quantify retinal thickness in the nine macular areas of the ETDRS grid. Retinal sensitivity was measured via microperimetry with a Macular Integrity Assessment Device (MAIA). The mean ages were 64.06 ± 11.98 years for the DM2 group and 60.79 ± 8.62 years for the control group. DM2 patients presented lower visual acuity ( The prevalence of diabetic retinopathy (DR) is growing worldwide, and it is estimated to increase to 51% by 2045 [DR is a microvasculopathy that induces changes in the inner retina, affects ischaemia, and increases blood-retina barrier permeability. Both vascular changes and diabetic neurodegeneration (DN) occur early in the disease, first affecting the retinal ganglion cell bodies and their dendrites, which can be detected as diffuse thinning of the ganglion cell layer (GCL) and inner plexiform layer (IPL) . Axons mThe structural changes in DR can be quantitatively analysed with new imaging techniques, mainly high-speed non-invasive optical coherence tomography (OCT), allowing the evaluation of the thickness and volume of the different retinal layers and the choroid ,6,7. ThiThe purpose of this study was to measure macular changes in the IRL thicknesses studied using swept-source OCT (SS-OCT) in type 2 diabetes mellitus (DM2) patients with moderate DR and without DME compared to those of healthy control individuals and to correlate them with retinal function evaluated via microperimetry to identify markers of retinal neurodegeneration prior to the appearance of DR.A total of 127 eyes were included in our study. Of these, 54 eyes were from DM2 patients, and 73 eyes were from healthy subjects. All eyes were evaluated at the Ophthalmology Department in the Lozano Blesa University Hospital in Zaragoza, Spain, from October 2021 to June 2022. All subjects underwent a complete ophthalmological exam in a single visit. The DM2 patients, which constituted Group 1, demonstrated a level 43 on the early treatment diabetic retinopathy study (ETDRS) classification [Exclusion criteria for both groups were amblyopia or best corrected visual acuity (BCVA) lower than 20/40 in the Snellen scale, spherical equivalent (SE) above ±5.50 diopters (D) or 3.00 D of astigmatism, any changes in pupillary reflex or ocular motility, intraocular pressure (IOP) over 20 mmHg or findings that suggested glaucoma, other macular diseases with macular impairment that lead to scotomas that affect vision, history of ocular surgery, corneal degeneration or lens opacity, the spectrum of vision loss related to dry eye disease, or the impossibility of collecting a good quality OCT profile. The electronic medical histories of the participants were deeply reviewed, looking for personal systemic pathologies. Patients with uncontrolled arterial hypertension, diagnosis of any metabolic syndrome, different form of DM, other systemic pathologies, or diagnosis or signs of neurologic or neurodegenerative disorders  were also excluded as patients with hormone replacement therapies.®, Carl Zeiss Meditec AG, Jena, Germany) images.All subjects underwent a complete ophthalmological exam in a single visit. For statistical purposes, BCVA was recorded with the 100% contrast ETDRS test as measured with the logarithm of the minimum angle of resolution (LogMAR). Axial length (AL) was calculated using an Aladdin KR-1 W Series optical biometry system  as the average of 5 measurements and expressed in mm. IOP was measured via Goldmann tonometry. The eye fundus was examined using Clarus widefield retinography , lipid profile, renal function parameters, and medication.®. Images whose quality scale (0 to 100) was lower than 60 were excluded. The different retinal layer and retinal thickness (RT) values were expressed in micrometres (μm) in the different sectors of the ETDRS grid with the 3D Macula protocol  using DRI-Triton SS-OCT (deep range imaging) . The software version was IMAGEnet 6 Version 1.22.1.14101protocol . The cenTo evaluate retinal sensitivity, third generation microperimetry (the Macular Integrity Assessment Device (MAIA); Topcon Corporation, Tokyo, Japan) was used for a complete evaluation with a 4–2 complete threshold strategy. To compare the MAIA and OCT thickness results, the sensitivity points generated with the microperimetry were divided into sectors. For an emmetropic eye, the MAIA 1° is equivalent to a circle with a diameter of 0.6 mm, the MAIA 3° is equivalent to a circle with a diameter of 1.8 mm, and the MAIA 5° is equivalent to a circle with a diameter of 3 mm. In the central ETDRS ring, we included the centre point and the 1° sensitivity points (0.6 mm diameter). In the 3 mm ETDRS ring, the 3° and 5° sensitivity points were located  in the 3 mm circle of the ETDRS grid . TherefoThe data were collected and exported to an Excel database .p < 0.05 indicated statistical significance for all the analyses.The values of the variables of interest for each patient were collected in an Excel database ver. 2016 . For the statistical analysis, the Statistical Package for the Social Sciences software  was used. First, a descriptive cross-sectional analysis of the sample with demographic variables and clinical characteristics was performed. Data normality was analysed with the Kolmogorov-Smirnov test. The parameters did not have a normal distribution, so differences between groups were analysed with the Mann–Whitney U test for independent samples, and the Spearman’s rank correlation coefficient test was conducted for bivariate analysis to correlate the variables of interest. A value of The sample size was calculated based on a preliminary study carried out by our group using the Epidat software (version 4.2.0.0). All calculations were performed using a two-sided test with an α risk of 5% (95% confidence level) and a β risk of 20% (80% power). A standard deviation of retinal thickness of 30 μm was estimated, wanting to detect differences of at least 16 μm, and setting a ratio between independent sample sizes of 1.5, a minimum sample size of 71 and 47 subjects per group was determined.p = 0.082). Regarding sex distribution, 20.4% and 39.7% were females and 79.6% and 60.3% were males in the DM2 and control groups, respectively. The mean time since DM2 diagnosis was 2.50 ± 2.88 years (0–11 years). The patients had adequate metabolic control of their disease, with a mean HbA1c of 7.58 ± 1.29%. A descriptive cross-sectional analysis of the sample determined that the mean age of the DM2 group was 64.06 ± 11.98 years (42–86 years) and that of the control group was 60.79 ± 8.62 years (42–83 years), with no differences between groups (p = 0.001). No differences were found between groups in AL (p = 0.075), SE (p = 0.110), or IOP (p = 0.676). The values are presented in BCVA reached significantly lower levels in the DM2 group (p = 0.010). Additionally, the analysis of different protocols revealed a significant decrease in the RNFL,specifically in the ON area. Thickness thinning was also observed in the IS, IT, and IN quadrant of the GCL+ protocol (GCL+IPL) ; and in the temporal quadrants as in ON and IS of the GCL++ protocol (ILM-IPL/INL (GCC), which corresponds to the GCL+ plus the RNFL thickness) in the DM2 group, as shown in Analysis of retinal thickness with SS-OCT revealed statistically thicker RT in the OT area in the DM2 group than in the healthy group  and total mean threshold , as shown in According to MAIA microperimetry, the retinal sensitivities were significantly higher in the control group than in the DM2 group, and there were differences in macular integrity . Additionally, the central ring for total RT and age were significantly positively correlated , as shown in Correlations between OCT findings (RT and RNFL thickness) and other parameters, including age, years of DM evolution, and glycaemic control, were studied using Spearman’s rank correlation coefficient test. Significant negative correlations were found between age and the outer ETDRS ring areas of RT, GCL +, and GCL++ . In addition, positive and significant correlations between MAIA sensitivities and GCL++ thickness were detected . No significant correlation was found between MAIA sensitivities and GCL+ thickness in any of the analysed sectors, as shown in Structural and functional correlations were demonstrated in the DM2 group. MAIA sensitivities and RNFL thickness were negatively correlated , there was no significant correlation between the RNFL and age, which may support ganglion cell loss before the RNFL is affected. Previous researchers, such as Rasheed et al., described an association between DR and diabetic neuropathy. In this study, patients with neuropathy showed significant thinning in the GC-IPL earlier than in the pRNFL. Similarly, Srinivasan et al. suggested that ganglion cell loss is a predictor of diabetic peripheral neuropathy .p = 0.033) and inferior quadrants  of RNFL thickness were negatively correlated with HbA1c levels.We could not confirm RNFL thickness deterioration with DR progression, diabetes progression time, or glycaemic variability. Contrary to our results, other researchers, such as Shi et al.  and Dashp = 0.037). Cholesterol is an important component of myelin and regulates membrane fluidity and signalling proteins. An increase in total cholesterol (TC) and LDL has been related to adverse effects on the RNFL [p = 0.007, and r = −0.292, p = 0.032, in the IT and C global sectors, respectively) and C global GCL+ and GCL++  were found by other researchers, such as Shi et al.  [p = 0.008). This has been postulated to be related to blood–brain barrier breakdown and the extravasation of immune cells through the vascular endothelium in other neurodegenerative diseases [We also analysed systemic risk factors  to determine their involvement in diabetic retinal changes. We excluded patients with poor control of their arterial blood pressure or a diagnosis of metabolic syndrome to avoid confounding factors. Our results revealed a significant positive correlation between LDL-C and RNFL  . HDL chodiseases . The invdiseases .p = 0.037; r = 0.307, p = 0.030; and r = 0.296, p = 0.037, respectively), which to our knowledge has not been determined previously in the literature. Similarly, previous studies have described a positive correlation between TG levels and INL thickness in DM1 subjects  [p = 0.035) [We also found that triglyceride (TG) levels were positively correlated with GCL+ thickness in the OS, II, and IS areas  . This ma= 0.035) . These fp = 0.001; r = 0.475, p < 0.001; and r = 0.448, r = 0.001, respectively) and negatively associated with filtrate rate (FR) deterioration . Previous studies have described retinal thinning as a biomarker of renal impairment in patients with diabetes (p = 0.009) [Contrary to our expectations, creatinine levels were positively correlated with the central area of the RNFL and the GCL+ and GCL++ thicknesses  . Srivast= 0.009) .Regarding the relationship between structural and functional findings, we correlated macular ETDRS grid areas with the corresponding microperimetry points. We did not contemplate GC displacement from their receptive, as evidence is not strong enough due to great variability between subjects ,32. AlthHowever, we have to consider the limitations of microperimetry, which include sources of variability such as fatigue and learning. Differences between right and left eye parameters related to fatigue have been described. This is because the duration of the test exceeds 5 min, and in convention, the right eye is analysed first . This coIn conclusion, our results suggest that the structure  and function  of the retina in patients with moderate diabetes display some changes. We demonstrated a correlation between the RNFL and retinal sensitivity measured with the MAIA, and the findings were not present when evaluating the GCL+. The diagnosis of GCL and RNFL thinning in DM2 patients without DR prior to the appearance of other DR signs would enable an accurate approach to this growing disease, with personalised assessment based on the DR course or stage. Future studies require a larger sample size, which should include patients in different stages of the disease and both DM1 and DM2 patients. Systemic risk factors are expected to be involved in retinal neurodegeneration in DM2 patients. However, the role of these factors remains largely unknown, and future lines of work should be promoted to determine it.


Uncontrolled blood pressure is an important medical and public health problem in developing countries like Ethiopia. Improving the management of hypertension requires a better comprehension of the factors influencing blood pressure control and the application of interventions. But in clinical practice, blood pressure is still not adequately controlled. Thus, this study aimed to assess uncontrolled blood pressure and associated among adult hypertensive patients on follow-up at public health facility ambulatory clinics in Bishoftu, Ethiopia.p-value < 0.05, statistical significance was proclaimed.A hospital-based cross-sectional study was conducted among 398 adult hypertensive patients who were on treatment and follow-up from April to May 31, 2022. Systematic random sampling was used to select study participants. Data were collected using an interviewer-administered, semi-structured questionnaire and chart review. The Eighth Joint National Committee (JNC 8) criteria was applied to define blood pressure control status. Binary logistic regression analysis was used to model the association between dependent and independent variables. An adjusted odds ratio and 95% confidence interval were used to measure the strength of the association. Finally, at a Of the total study participants, 249(62.6%) were male. The mean age was 62.26 ± 11.55 years. The overall proportion of uncontrolled blood pressure was 58.8% (95% CI: 54–64). Salt intake , lack of physical activity , habitual coffee consumption , higher BMI , and non-adherence to antihypertensive medications  were independent predictors of uncontrolled blood pressure.More than half of the hypertensive patients in this study had uncontrolled blood pressure. Healthcare providers and other accountable stakeholders should urge patients to follow salt restriction, physical activity, and antihypertensive medication regimes. Reduced coffee consumption and weight maintenance are other crucial blood pressure control measures. Hypertension (HTN), the underlying cause of numerous bodily system and organ failures, continues to be a major global concern and public health issue , 2. It wHypertension affects almost a billion people globally, with two-thirds of those people living in low-income nations . One-thiControlling HTN within a targeted blood pressure (BP) goal is crucial for lowering related morbidity and mortality. BP is deemed controlled when it is less than 150/90 mmHg with regular use of antihypertensive medication(s) for individuals aged 60 years and above and less than 140/90 mmHg in patients younger than the age of 60 years and all ages of hypertensive patients with diabetes and/or chronic kidney disease , 11. In Patients with uncontrolled BP have a higher risk of heart failure and mortality from cardiovascular complications of HTN . Long-teGlobally, little is known about how well hypertensive patients control their BP and what factors contribute to poor BP control. According to previous studies, patients with HTN who have uncontrolled BP have a variety of contributing factors. Sex, age, occupation, duration since hypertension diagnosis, poor medication adherence, lack of exercise, salt intake, being overweight or obese, presence of comorbidity, and alcohol consumption were all linked to poor BP control –21.The prevention of complications from HTN greatly depends on the recognition of the problems in BP control and the implementation of solutions , 16, 20.The present study involved both hospitals and primary healthcare facilities, but most prior studies were conducted in one of these settings. While several studies have shown the magnitude and correlates of HTN, findings on the magnitude and factors that influence BP control among hypertensive patients on treatment and follow-up are lacking. Furthermore, the factors that contribute to uncontrolled BP are inconsistent across studies, and no study was conducted in the study setting among HTN patients to assess their BP control status. Thus, this study aimed to determine the level of uncontrolled BP and associated among adult hypertensive patients on follow-up at public health facility ambulatory clinics in Bishoftu town, Ethiopia.A hospital-based cross-sectional study was conducted from April to May 31, 2022, in Bishoftu town. Bishoftu town is 47 km away from Addis Ababa and divided into 14 administrative kebeles. As of the 2007 national census, Bishoftu had a total population of 99,928 . There are six health centers and two hospitals in the town. The current study was conducted in four health centers and two hospitals, namely Bishoftu Health Center, Cheleleka Health Center, Babogaya Health Center, Keta Health Center, Air Force Hospital (AFH), and Bishoftu General Hospital (BGH).The source population was all patients with hypertension who were on follow-up at public health facility ambulatory clinics in Bishoftu town. The study populations were all hypertensive patients who were on follow-up at selected public health facility ambulatory clinics in Bishoftu town during the study period.All hypertensive patients over the age of 18 who had been on follow-up at the selected public health facilities for at least 6 months and came to the outpatient department of medicine for follow-up visits during the study period.Hypertensive pregnant women, patients with cognitive impairment, newly diagnosed patients, patients with hypertensive urgency or emergency, patients who were seriously ill at the time of data collection and unable to respond to the questions, patients who declined to participate in the study, and those whose medical records lacked information on their demographics and blood pressure were all excluded.p = 0.37) taken from a previous study done in Nekemte Referral Hospital [n = the required sample size, Z α/2 = the standardized normal distribution curve value for the 95% confidence interval, p = the proportion of uncontrolled blood pressure, and d = the margin of error between the sample and population.The sample size was calculated using single population proportion formula with the assumptions of the magnitude of uncontrolled hypertension .Smoking, alcohol drinking status, khat chewing, physical exercise, eating vegetables and fruit, salt intake, and habitual coffee consumption.Duration of anti-hypertensive treatment, adherence to anti-hypertensive drugs, treatment modification, side effects, class of anti-hypertensive drugs, and the number of medications.Defined as Systolic blood pressure of ≥ 150 mmHg and/or Diastolic blood pressure of ≥ 90 mmHg with regular use of antihypertensive medication(s) for individuals age 60 years and above and Systolic blood pressure of ≥ 140 mm Hg and/or diastolic blood pressure of ≥ 90 mmHg) in patients younger than the age of 60 years and all ages of hypertensive patients with diabetes and/or chronic kidney disease [BP measurements made by a physician who monitored hypertensive patients during their last six months follow-up visits were reviewed in the charts of adult hypertensive patients. The last BP was measured using a pretested standard mercury sphygmomanometer by trained data collectors. BP cuff with the proper cuff size, which covered two-thirds of the upper arm, while the patient was in a sitting position with 90-degree back support, rested for no less than five minutes, and avoided caffeine and cigarettes for 30 min before the measurement. Extra clothing that might interfere with the BP cuff has been removed. With a bare arm and the middle of the cuff at heart level, and uncrossed legs, without talking during or between measurements. During the measurement, the patients were kept relaxed. The BP cuff was inflated to the point where no noises were detected through the stethoscope. The cuff is then progressively deflated to measure the systolic and diastolic blood pressures. Two measurements were performed back-to-back with a minimum 5-minute gap, and the mean BP was recorded , 23.Medication adherence was assessed with the Hill-Bone Compliance to High Blood Pressure Therapy Scale (HB-HBP) medication adherence subscale. The subscale has nine items with a four-point Likert-type scale: "none of the time," "some of the time," "most of the time," and "all of the time." The total scores range from 9 to 36, with higher scores reflecting poorer adherence to antihypertensive medication. Patients were deemed to be adherent if their scores were at or above the median –26.Smoking was assessed by one item whether the patients smoked or even a puff in the last seven days. Patients were classified as non-smokers if they had not smoked or had not taken even one puff in the last 7 days .Male patients who drank more than 2 units of alcohol per day and female patients who drank more than 1 unit of alcohol per day were considered alcohol consumers , 19.Were assessed and grouped according to the number of days they ate each per week into three: those who ate for less than one day per week (none), 1–3 days per week, and 4–7 days per week .Information on habitual coffee intake was collected with 1 item: "How many days of the week do you drink coffee?" Participants were defined as "coffee drinkers" if they drank coffee three or more times per week; otherwise, they were regarded as "non-drinkers" .Physical activity was assessed by asking how many minutes per day and days per week a patient spent doing physical activity. This physical activity includes jobs or sports that require moderately intense activity that only slightly increases breathing or heart rate, such as cycling, swimming, volleyball, dancing, farming, gardening, and housework. It also includes activities like brisk walking, carrying light loads, swimming, and dancing. If the participants engaged in physical activity for at least 30 min per day, at least five days a week (≥ 150 min per week), they were considered physically active , 29, 30.Twelve items were used to measure the low-salt diet. After the mean was calculated, a patient is considered adherent to the low salt diet if they scored ≥ 6 .Data were collected using a semi-structured interviewer-administered questionnaire and document review. The questionnaires were adapted from validated scales and published articles and modified for the study's context , 31, 32.n = 20) at non-selected public health facilities, and a correction was made accordingly. Two days of training were organized for data collectors and supervisors on the procedure of data collection and the purpose of the study. All collected data were examined for completeness and consistency during data management, storage, and analysis.The English version of the questionnaire was prepared. Then it was translated into Amharic and Afan oromo versions  and back to English to ensure consistency. To ensure the quality and consistency of the data abstraction format and the questionnaire with the objective of the study, a pre-test was done on 5% of the total sample of patients  with a 95% confidence interval (CI) was used to determine predictors of uncontrolled blood pressure. At this level, a p-value of < 0.05 was considered statistically significant.Data were coded and entered into Epi-Info Version 7 and exported to the Statistical Package for Social Sciences (SPSS) Version 26 for cleaning and statistical analysis. Normality assumptions for continuous variables were checked using the Shapiro–Wilk test. To explain the study population with relevant variables, descriptive statistics were used. Binary logistic regression analysis was used to model the associations between uncontrolled blood pressure and independent variables. The statistical assumptions for binary logistic regression, i.e., multi-collinearity, normality, linearity, independence of residuals, and outliers, were assessed, and no significant violations were identified. The regression model was fitted using the standard model-building approach. The goodness of fit of the final model was checked using the Hosmer and Lemeshow test, and the result was significant with a A total of 398 adult hypertensive respondents were interviewed, making up a 100% response rate. The mean age of the participants was 62.26 (SD: ± 11.55) years, with a minimum age of 35 and a maximum age of 89 years. Two hundred forty-nine (62.6%) of the respondents were male, 282 (70.9%) were married, and 328 (82.4%) were urban residents. The majority of them, 147 (36.6%), attended secondary school, and 164 (41.2%) had a monthly income between 2000 and 4000 Birr  participants had a family history of HTN, and 148 (37.2%) of them were diagnosed with HTN between 5 and 10 years. Of the participants, 171 (43%) had a history of missed follow-up, and 195 (49%) measured their BP monthly. About 152 (38.2%) had a comorbid illness, and of those, 44.2% had diabetes. Moreover, 188 (47.2%) had BMI measurements within the normal range  were current smokers, and 184 (246.2%) were habitual coffee drinkers. Among the study participants, 253 (63.6%) did not eat vegetables, and 277 (69.6%) did not eat fruits 1–3 days per week  received their medication free of charge, and 109 (27.4%) have been on antihypertensives for more than ten years. About 130 (32.7%) participants reported experiencing side effects, and weakness was the most common side effect due to medications. Thiazide diuretics were the most widely used anti-hypertensive medications, comprising 36.7% . The highest and lowest levels of uncontrolled blood pressure were found in Keta and Babogaya Health Centers, respectively Fig. .Fig. 2Blp-value < 0.25 in the bivariate analysis were chosen as candidate variables for the final model. Hence, in the bivariate analysis, age, family history of hypertension, duration of HTN diagnosis, higher BMI, habitual coffee consumption, salt intake, lack of physical activity, duration of therapy, number of medications, and non-adherence to antihypertensive medications showed statistically significant associations with uncontrolled BP. Following adjustment for potential confounding factors with multivariable binary logistic regression analysis, salt intake, lack of physical activity, habitual coffee consumption, higher BMI, and non-adherence to antihypertensive medications were independent predictors of uncontrolled BP at a p-value < 0.05.After the model has been checked for multi-collinearity and model fitness; variables with a Hypertensive patients who added salt to their food had 2.5 times greater odds of uncontrolled BP compared to hypertensive patients who used no salt in their food . The odds of uncontrolled BP among hypertensive patients not involved in physical activity were 1.4 times greater compared to hypertensive patients involved in physical activity . Compared to non-coffee-drinking hypertensive patients, those hypertensive patients who were habitual coffee consumers had 4.5 times the odds of having uncontrolled BP . Hypertensive patients with higher BMI (overweight and/or obese) had two times greater odds of uncontrolled BP compared to those who were normal . Furthermore, patients who were non-adherent to their anti-hypertensive drugs had 2.3 times greater odds of uncontrolled BP than those who were adherent  . This is in line with studies conducted in Tikur Anbesa General Specialized Hospital, Addis Ababa (59.9%) , Debre TThese differences could be explained by the fact that in our study, the majority of the patients had regular follow-up visits at a dedicated health facility, as well as the difference in study design and sample size. Furthermore, the disparity could be attributed to sociocultural and behavioral differences among the study population as well as differences in the expertise of healthcare professionals involved in the management of HTN and healthcare services in the study settings. In addition, the inconsistency may also be linked to differences in antihypertensive drug adherence rates and variations in the criteria utilized to classify hypertensive patients as having uncontrolled or controlled BP. Most studies used the JNC7 guideline , which eIn this study, hypertensive patients who added salt to their food had 2.5 times higher odds of uncontrolled BP compared to hypertensive patients who used no salt in their food. This finding is consistent with studies from the University of Gondar Referral Hospital and Debre Tabor District Hospital in Northwest Ethiopia , 20, whiPhysical activity was another significant factor associated with uncontrolled BP. In this study, the odds of uncontrolled BP among hypertensive patients not involved in physical activity were 1.4 times greater compared to those of hypertensive patients involved in physical activity. This finding is similar to studies conducted at Ayder Comprehensive Specialized Hospital in Tigray, Ethiopia ; NekemteIn this study, in comparison to non-coffee-drinking hypertensive patients, habitual coffee users had 4.5 times the odds of having uncontrolled blood pressure. This is similar to a study conducted in Spain  which shThis study revealed that hypertensive patients who were overweight and/or obese had two times higher odds of uncontrolled BP compared to those who were normal. This finding is in agreement with studies done at Jimma University Teaching and Specialized Hospital, Ethiopia ; Ayder CAdherence to medications is critical for preventing the effects of HTN-related morbidities and mortality. One of the main causes of poor BP control is poor medication adherence, which also affects the efficacy of health outcomes broadly and dampens the optimal therapeutic values. In line with studies conducted in Nekemte Referral Hospital, Western Ethiopia ; Debre TDue to the cross-sectional study design used in this study, it is impossible to determine temporal relationships and difficult to confirm the causal-effect relationship between the dependent and predictor variables. The classes of drugs used and their impact on BP control was not investigated in detail. Moreover, there might be recall and social desirability biases since the study participants' behavioral practices were based on self-reports, and the performance of these behaviors was not observed or validated.In conclusion, the proportion of hypertensive patients with uncontrolled BP was relatively high in the study setting. Salt intake, lack of physical activity, habitual coffee consumption, higher BMI, and non-adherence to antihypertensive medications were factors associated with uncontrolled BP. Maintaining controlled BP is critical to avoiding the effects of uncontrolled BP. Healthcare providers and other responsible stakeholders should encourage patients to adhere to antihypertensive medications, physical activity, lifestyle modification, and adherence counseling measures to successfully control BP. Furthermore, studies using physical and biochemical markers to pinpoint the most significant factors linked to BP control, impediments to successful BP control, and treatment options to enhance treatment results are recommended.


Respiratory failure from tick paralysis (TP) is an important cause of mortality in cats and dogs in Australia, occurring from a combination of respiratory muscle paralysis, upper respiratory tract obstruction and pulmonary disease. Patients may require positive-pressure ventilation in management of any combination of hypoxemia, hypoventilation or respiratory fatigue, but may also require airway management due to laryngeal paralysis. No single ventilation strategy is recommended due to the heterogenous disease presentations. Lung protective ventilation should be used in patients with pulmonary disease. Due to local and systemic effects of TP, patients are at higher risk of complications such as aspiration pneumonia and corneal ulceration and may have additional intravenous fluid and nutritional considerations. Treatment with hyperimmune serum is associated with improved outcomes. Prognosis is considered good with documented survival to discharge (STD) of 52.6–77% for animals with TP ventilated with lung disease and 90.5% for animals without lung disease. Median reported duration of ventilation for TP ranges from 23 to 48 h (range 3 h−10 days). The severity of individual neuromuscular signs and the presence of associated conditions such as aspiration pneumonia and laryngeal paralysis may necessitate longer periods of mechanical ventilation. This review aims to summarize the current recommendations regarding indications, management and prognosis of cats and dogs undergoing MV for TP and to identify areas for future research. Tick paralysis (TP) is a cause of morbidity and mortality in dogs and cats, with >10,000 pets estimated to present to veterinary clinics for treatment annually  is an important intervention in cats and dogs severely affected by TP. The objective of this review is to summarize the current recommendations regarding indications, management and prognosis of cats and dogs undergoing MV for TP and to identify areas for future research.I. holocyclus and I. cornuatus, with each occupying a distinct geographical location. Ixodes holocyclus populates the coastline of Queensland and New South Wales with a small number of cases documented in Eastern Victoria ., 17.1, 1Proposed mechanisms of respiratory compromise include respiratory muscle paralysis in isolation or combination with upper respiratory tract (URT) obstruction , 19, cenn = 25)  . Severe n = 25) . Anothern = 25) .The primary cause of bronchopneumonia in animals with TP is believed to be aspiration , 9. The A study of five dogs with TP demonstrated that the protein concentration of edema fluid was less than half the serum protein concentration. The authors proposed these findings were consistent with hydrostatic PE secondary to toxin-related cardiac dysfunction . AnotherA combined retrospective and prospective study of lung histopathology in fatal TP demonstrated evidence of high protein oedema and fibrin exudation in 100% 23/23) and 69.6% (16/23) of dogs and 100% (11/11) and 90.7% (10/11) cats, respectively , 23. Whe/23 and 6Vomiting and regurgitation are common presenting signs of tick paralysis in dogs and cats , 24. RegAcute management of TP involves intravenous administration of tick anti-serum (TAS), clipping of the coat and topical application of a rapid kill acaricide to locate and remove any remaining ticks , 28. SerSupportive care should be tailored to individual patient needs and may consist of intravenous fluid therapy, supplemental oxygen, sedation, medicated ocular therapies, physiotherapy, bladder management, prokinetics and proton pump inhibitors , 28, 30.In depth discussion of the management of animals with TP but without respiratory failure is beyond the scope of this review and the author directs the reader's attention to the recent clinical guidelines provided by an expert advisory panel .2) >60 mmHg] despite therapy or when severe hypoxemia [arterial partial pressure oxygen (PaO2) <60 mmHg or peripheral oxygen saturation (SpO2) < 90%] persists with supplemental oxygen. Unsustainable respiratory effort with concern for impending respiratory arrest is another important indication and is a subjective assessment based on clinical judgement  of dogs were ventilated for hypoxemia, 33.3% (18/54) for hypercapnia, 18.5% (10/54) for unsustainable breathing effort and 7.4% (4/54) for fatigue resulting in respiratory arrest . Cats we2) and the end tidal CO2 (ETCO2) obtained via capnography are accepted surrogate markers for PaCO2 in the absence of increased physiological dead space, returning values 2–10 mmHg higher and lower than PaCO2, respectively  and cricothyrotomy (CTT) tubes are recommended in animals with generalized LMN disease requiring long-term ventilation  or to faWhen considering a patient for a surgical airway, a clinician should weigh the risk and costs of TT/CTT against the expected time and cost of continued MV. A surgical airway in TP patients is indicated to facilitate weaning in animals that are expected to fail extubation due to ongoing laryngeal paralysis , 52, 54.One case report describes the successful use of a cricothyrotomy tube in a dog undergoing MV for TP and aspiration pneumonia that failed weaning due to persistent laryngeal paralysis . This wa2) and employ lung protective strategies by administration of set tidal volumes, inspiratory pressures, and positive end expiratory pressure (PEEP)  . If an Ie (PEEP) . Intubate (PEEP) . In anim targets . Humidifn system .Dogs and cats mechanically ventilated for pulmonary parenchymal disease have higher mortality rates (23–47.4%) than those receiving positive pressure ventilation (PPV) for ventilatory failure 9.5%) , 31. Wit.5% , 31.General anesthesia is typically required to facilitate invasive mechanical ventilation. Total intravenous anesthesia (TIVA) is preferred as inhalant anesthesia  may causCombinations of opioids, benzodiazepines, and anesthetic agents, including propofol and ketamine, have been described in small animals with good success , 63. A sWhile midazolam is frequently used in TIVA protocols, withdrawal syndromes are associated with long-term benzodiazepine use in humans and are an important consideration for patients receiving long term mechanical ventilation. Signs of withdrawal develop within 48 h of discontinuation of therapy and have been associated with agitation, muscle twitching, disorientation, and seizures, with an overall higher prevalence in children , 65. MidComparative studies are needed to determine whether the functional neuromuscular blockade caused by holocyclotoxin allows for lower anesthetic doses in patients with TP. As naturally occurring lower motor neuron paralysis is present, neuromuscular blocking agents may not provide additional ventilatory control and their use should be carefully considered with appropriate troubleshooting for other causes of patient-ventilator asynchrony.2) between 80 and 120 mmHg and a partial pressure of arterial carbon dioxide (PaCO2) between 35 and 50 mmHg  8 ml/kg and PEEP 5 cmH2O as initial settings  modes of ventilation have been described for use in TP , 30, howsettings . While gsettings , 70.Patients with pulmonary parenchymal disease have reduced lung compliance and may require more aggressive ventilator settings than patients with ventilatory failure alone . PPV is 2O, tidal volumes > 10 ml/kg and cyclic alveolar opening and closing are the main determinants of VILI in humans   of 5 and 7 cmHphy (CT) . At 15 coccurred . These f2O) to promote alveolar recruitment and reduce sheering injury  . While mg injury , 77. Perg injury . Additioigh PEEP . Pilot sigh PEEP  and therigh PEEP , 81.20 PEEP and Vte 15 ml/kg with or without 5 cm H2O PEEP  mismatch may benefit from alveolar recruitment maneuvers (ARMs) , 82, 83.elow 92% . Variouselow 92% , 86. Traelow 92% , increaselow 92% , 82–84 aelow 92% . To the An invasive, mandatory mode of ventilation is recommended initially to provide airway protection and relieve work of breathing in patients experiencing neuromuscular paralysis and potentially respiratory fatigue, respectively . Most exContinuous spontaneous ventilation modes (such as pressure support ventilation) are most suited to patients with reduced ventilatory capacity and normal respiratory drive. This mode is unlikely to be appropriate in the initial phases but should be considered in patients recovering from respiratory paralysis (such as those with TP) and when assessing suitability for weaning , 90.2) of 1.0. Once the patient is stable a gradual reduction in FiO2 is typically the first adjustment made, with the goal of reducing inspired oxygen below the threshold for toxicity (<0.6)  . Followi2O  , 88 and Successful management of the ventilated patient requires continuous monitoring and exemplary nursing care. At a minimum, electrocardiography (ECG), blood pressure, pulse oximetry and capnography should be continuously monitored, as spontaneous breathing cannot be reliably observed .Although technically challenging, placement of an arterial catheter is recommended for real-time hemodynamic monitoring and ease of sampling for arterial blood gas analysis, as retrospective analysis of ventilated dogs demonstrated pulse oximetry to be an insensitive measure of hypoxemia . Multi-lContinuous and exemplary nursing care is crucial for the successful management of patients undergoing MV , 98. CarICU hospitalization  and gene2 for 2 min prior to oral and ETT care.Oral lesions have been reported in 37–90.5% of dogs receiving orotracheal MV , 101. ThFacial nerve paralysis , megaesoPulmonary oedema is a prominent feature in animals with TP, however the underlying mechanism for its development remains poorly understood –10, 16. High protein alveolar fluid and fibrin deposition was identified in pulmonary histopathology of cats and dogs that died from TP without obvious evidence of bronchopneumonia. The authors postulated these changes were suggestive of increased permeability oedema and an acute inflammatory process or lung injury . Given tThe apparent need for judicious fluid therapy in these patients does not preclude its use entirely. Animals with TP are routinely kept nil per os  until clinical signs resolve , placingNutritional support is recommended for patients in caloric deficit for >72 h . MalnutrIn mechanically ventilated patients, nutrition may be delivered enterally or parenterally . Provisivia a dedicated port in single or multi-lumen jugular or long-stay peripheral catheter and contraindications include inappropriate vascular access, uncontrolled diabetes mellitus and hypervolemia  tube is a minimally invasive and cost-effective  of continuous positive airway pressure applied , including non-survivors from cardiopulmonary arrest and euthanasia , 118. A MV can be used to successfully manage respiratory failure in cats and dogs with TP, with reported survival rates of 52.6–77 and 90.5% in animals with diseased and healthy lungs, respectively , 31. DesMV is an important treatment modality in cats and dogs suffering respiratory failure from TP , 52, 118TO'K and RD performed research, manuscript preparation, and editing. All authors contributed to the article and approved the submitted version.


Acute kidney disease (AKD) is believed to be involved in the transition from acute kidney injury (AKI) to chronic kidney disease in general populations, but little is understood about this possibility among kidney surgical populations. This study aimed to elucidate the incidence of AKD after partial nephrectomy and risk factors that promote the AKI to AKD transition.From January 2010 to January 2020, this study retrospectively collected a dataset of consecutive patients with renal masses undergoing partial nephrectomy in 4 urological centers. Cox proportional regression analyses were adopted to identify risk factors that promoted the AKI to AKD transition. To avoid overfitting, the results were then verified by logistic least absolute shrinkage and selection operator (LASSO) regression. A nomogram was then constructed and validated for AKI to AKD transition prediction.AKI and AKD occurred in 228 (21.4%) and 42 (3.9%) patients among a total of 1062 patients, respectively. In patients with AKI, multivariable Cox regression analysis and LASSO regression identified that age , baseline eGFR , RENAL score , ischemia time > 30 min , and intraoperative blood loss > 300ml  were risk factors for AKD transition. These five risk factors were then integrated into a nomogram. The nomogram showed excellent discrimination, calibration, and clinical net benefit ability.Around 3.9% patients following partial nephrectomy would transit from AKI to AKD. Intraoperative blood loss and ischemia time need to be diminished to avoid on-going functional decline. Our nomogram can accurately predict the transition from AKI to AKD.The online version contains supplementary material available at 10.1186/s12894-023-01325-3. Partial nephrectomy (PN) should be adopted for renal masses whenever possible to maximally protect renal function . NeverthBoth AKI and CKD have been well-defined to improve research efforts and refine subsequent management strategies and recommendations . HoweverSimilar to AKI, AKD is divided into four stages based on serum creatinine levels 7–90 days after the first insult . For medThus, this study aimed to elucidate the incidence of AKD after PN, identify the risk factors that promote AKI transiting to AKD, and construct a risk model to predict the transition from AKI to AKD in renal surgery patients.Our study protocol was approved by the institutional review board of the Institutional Review Board of the Second Affiliated Hospital of Chongqing Medical University Ethical Committee and registered in the Chinese Clinical Trial Registry (Registration No.: ChiCTR2000034080 (23/06/2020)). Informed consent was waived due to its retrospective design in the training cohorts. And Informed consent was obtained in the validation cohorts. We routinely produced PN with main-artery clamping and warm ischemia technique.2 (n = 12); (3) solitary kidney(n = 28); 4)unavailable renal function data between 7 and 90 days (462); and (4) conversion to radical surgery or an additional radical surgery during the surgery or 30 days after surgery (n = 80). A prospective cohort with the same criteria  served as validation (n = 186). All patients were typically followed up every 1–3 months for the first 1 year and then every 6–12 months per year, including eGFR and renal imaging (sonograph or CT scan).Figure Demographic characteristics, surgical outcomes and kidney functional results during follow-up were collected from the electronic databases in 4 centers  and filled into a predesigned standardized sheet. AKI was defined according to the KDIGO serum creatinine criteria as increase in serum creatinine by ≥ 0.3 mg/dL (≥ 26.5 micromol/L) within 48 h, or increase in serum creatinine to ≥ 1.5 times baseline, which is known or presumed to have occurred within the prior seven days, or urine volume < 0.5 mL/kg/hour for six hours . AKD wasData are expressed as the mean ± standard deviation or medians (interquartile ranges) for continuous variables and as the percent frequency for categorical variables. During the comparison study between patients with and without AKI, continuous variables were compared using Student’s t test or the Wilcoxon rank sum test, while categorical variables were compared using the chi-square test between the two groups. Univariable and multivariable Cox regression analyses were adopted to identify risk factors for AKD. The results were then verified by logistic least absolute shrinkage and selection operator (LASSO) regression, a machine learning method, to avoid overfitting and underpowering. Kaplan–Meier analysis was used to analyze relationships between AKD transition and ESKD during the long-term follow-up. A nomogram was created to visualize the prediction. The constructed nomogram was then assessed by discrimination (concordance index [C-index]), calibration  and decision curve analysis. STATA version 16.1 software  was used for the data analysis. A difference of p < 0.05 indicated statistical significance and the level of precision was present according to EUA guideline .2), with a higher rate of ischemia time over 30 min (26.2% vs. 14.9%), and had more intraoperative blood loss (210 ± 103ml vs. 160 ± 92ml). The demographic information and surgical outcomes are presented in Table AKI and AKD occurred among 228 21.5%) and 42 (3.9%) patients, respectively. Patients with AKD were identified as older (57.7 ± 13.5 vs. AKI group: 54.2 ± 11.7), with a higher eGFR (131.2 ± 42.8 ml/min/1.73 m^2 vs. the AKI group: 120.8 ± 30.9 ml/min/1.73 m.5% and 4After the PH (Schönfeld test) test, univariable and multivariable Cox regression analyses identified that age , baseline eGFR , RENAL score , ischemia time > 30 min , and intraoperative blood loss > 300ml  were risk factors for AKD transition  with the same criteria (from 2020.01 to 2021.06) was served as validation. The predictive ability was 0.903. Calibration plot and DCA also showed excellent outcomes.  and the surgical experience were not collected from our database. In addition, potential risk factors  were not accessible during the follow-up. Proteinuria was proved to be strongly correlated with postoperative AKI, functional decline .In conclusion, our study found that the overall incidence of AKD in the surgical population is low. Modifiable risk factors  should be diminished as possibly as a surgeon can to avoid on-going functional decline as they were the only modifiable risk factors for AKD, i.e. open surgery or surgeons with more expertise should be considered for complex renal mass to diminish ischemia time and blood loss. A close follow-up for patients with high-stage AKD should be implemented, and possible interventions should be evaluated in future studies to break the AKI-AKD-CKD course to prevent long-term renal functional deterioration after PN.Below is the link to the electronic supplementary material.Supplementary Material 1