Textbook case, little to add. Microhematuria, proteinuria and sensorineural hearing loss in a young male with a family history of women with hematuria = Alport syndrome.

Textbook case, little to add. Microhematuria, proteinuria and sensorineural hearing loss in a young male with a family history of women with hematuria = [HIDDEN].

24-year-old male presenting with dysmorphic microhematuria, proteinuria of 3 g/24 h, eGFR (CKD-EPI) 85 ml/min and sensorineural hearing loss. He reports that his maternal grandmother required dialysis at 70 years of age and both his mother and younger sister have isolated microhematuria. Which of the following diseases is more likely?

Autosomal dominant polycystic kidney disease.

Polycystic kidney disease complicates renal pathology in a family with Fabry disease.

Fabry disease is a rare lysosomal storage disorder that primarily affects the heart and kidneys, often presenting with reduced renal function. Polycystic kidney disease is a renal condition in which cysts are found, which have a different presentation than the cysts associated with Fabry disease. We report a 60-year-old male patient who was diagnosed with Fabry disease with the classic c.730G > A (p.Asp244Asn) variant of the <iGLA</i gene at 34 years of age. Fabry symptoms in this patient include hypohidrosis, hearing loss, corneal whorling, and edema. He also presented with polycystic kidney disease with multiple simple and mildly complex cysts on abdominal ultrasound. Family history of note included Fabry disease in his mother and maternal uncle as well as polycystic kidneys in his mother. Molecular analysis for polycystic kidney disease revealed a variant of uncertain significance (VUS) in the <iPKD1</i gene. Although the in silico studies of this VUS have inconclusive results, the patient fills clinical criteria of autosomal dominant polycystic kidney disease, therefore, Fabry disease and polycystic kidney disease are considered two co-existing manifestations in this family. This case demonstrates the possibility of two renal comorbidities in the same individual and the risk of one diagnosis being overlooked by the other.

Autosomal dominant Alport's syndrome: study of a large Tunisian family.

Alport's syndrome is a hereditary nephritis that may lead to end-stage renal disease (ESRD) in early adult life. It is a clinically and genetically heterogeneous nephropathy. Alport's syndrome is often associated with sensorineural deafness and/or ocular abnormalities. In contrast with the well-known X-linked phenotype, very little is known about the autosomal dominant form caused by mutations in COL4A3 and COL4A4 in the chromosome region 2q35-q37. We describe a Tunisian family with autosomal dominant Alport's syndrome in which males and females were equally affected. Two members reached ESRD at age 40 and 53 years, respectively. Three members experienced isolated microhematuria and one member experienced sensorineural deafness. No eye abnormalities were observed. Immunohistochemical studies showed a normal distribution of the alpha5 (type IV collagen) chain in the epidermal basement membrane. Genetic analysis demonstrated that a common haplotype co-segregated with the disease in the heterozygous state in all affected patients, thereby, confirming an autosomal dominant mode of inheritance. The same haplotype was observed in two asymptomatic children. We conclude that autosomal dominant Alport's syndrome, follows a rare mode of inheritance and exhibits a milder phenotype than usually observed in classic X-linked Alport's syndrome. The frequency of this mode of inheritance should be confirmed by a larger study.

A case report on the exceptional coincidence of two inherited renal disorders: ADPKD and Alport syndrome
.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of dialysis-requiring end-stage renal disease in adults and is characterized by the slowly progressing replacement of renal tissue by focal macrocysts. Alport syndrome (AS; hereditary nephritis) is a rare, inherited disorder of the basement membrane associated with hematuria, proteinuria, and loss of kidney function as well as sensorineural hearing loss and ocular abnormalities. Here, we report on a family in which both ADPKD and AS are present. In a male patient, both -ADPKD and AS coincided. This patient shows the very rare coexistence of two severe, inherited renal disorders and illustrates the importance of considering additional diagnoses in the setting of positive family history for a common hereditary disorder.
.

[From Alport syndrome to benign familial hematuria: clinical and genetic aspect].

Alport syndrome (AS) is a hereditary glomerulonephritis variably associated with neural hearing loss and ocular abnormalities. The prevalence of the disease is estimated at approximately 1 in 50,000 live births. AS arises from mutations in genes encoding alpha chains constituting type IV collagen. In 85% of patients, the disease results from mutations in the COL4A5 gene located on X chromosome. In the hemizygous male, persistent microhematuria is present from early life, then proteinuria and renal insufficiency occur with time, leading to end-stage renal failure before age 40. In the heterozygous female, clinical manifestations vary from completely healthy state to end-stage renal failure, most often reached after the age of 40. In 15% of patients, the disease results from mutations in either the COL4A3 or the COL4A4 gene, both located on chromosome 2. When both alleles are mutated (autosomal recessive form), the phenotype is constantly severe, resembling that of the hemizygous male in the X-linked form. In the heterozygous individual, the clinical spectrum vary from the absence of any manifestation to the development of proteinuria - the so-called autosomal-dominant AS -, and even renal insufficiency, sometimes reaching end-stage (after the age of 40) through the most frequently encountered phenotype, i.e. a persistently isolated microhematuria, accounting for the so-called benign familial hematuria (or healthy carrier state). The determinants of the phenotype remain largely unknown, so that it may be risky to predict renal prognosis in the individual with a single COL4A3/A4 mutation and an isolated microhematuria at the time of examination.

A familial case of mitochondrial disease resembling Alport syndrome.

A 38-year-old man with mild sensorineural hearing loss, diabetes mellitus, proteinuria, and slight renal dysfunction was admitted to our hospital for a renal biopsy to determine the cause of kidney disease. His elder sister and mother also had sensorineural hearing loss and renal failure, suggesting the existence of a common genetic disease in this family. Although the clinical features of the patient were similar to features of Alport syndrome, renal biopsy revealed no sign of Alport syndrome. We next considered a possibility of a mitochondrial kidney disease described by Jansen in 1997. Indeed, genetic analysis of mitochondrial DNA clarified the existence of A3243G mutation in the patient and his sister. This syndrome should be recognized by nephrologists as a differential diagnosis of Alport syndrome, diabetic nephropathy, and primary glomerular diseases.

Living donor kidney transplantation in patients with hereditary nephropathies.

Patients with some hereditary nephropathies-including autosomal dominant polycystic kidney disease (ADPKD), Fabry disease and Alport syndrome-can progress to end-stage renal disease (ESRD) and are candidates for kidney transplantation. When considering whether a potential living donor is appropriate for a particular patient, clinicians should be aware of the increased risk of adverse outcomes for the donor and the recipient. Renal transplantation from a living related donor is not contraindicated in most nephropathies that have an autosomal recessive mode of inheritance (for example, autosomal recessive polycystic kidney disease and cystinosis). Renal transplant recipients with ADPKD, however, should only receive a kidney from a related donor if the disease has been excluded in the donor by imaging and/or genetic testing. Potential living related donors for patients with Alport syndrome should be evaluated carefully for the presence of microhematuria and microalbuminuria before a decision is made to perform transplantation, and mothers or heterozygous sisters of affected male recipients with X-linked Alport syndrome should be informed about the possible long-term increased risk of renal dysfunction associated with donation. Most patients with atypical hemolytic uremic syndrome should not receive a kidney transplant from a living donor because there is a high risk of disease recurrence and graft loss.

Family History is Important to Identify Patients with Monogenic Causes of Adult-Onset Chronic Kidney Disease.

Monogenic causes of chronic kidney disease (CKD) are more prevalent in adults than previously thought, as causative gene variants are found in almost 10% of unselected patients with CKD. Even so, genetic testing in patients with adult-onset CKD is uncommon in clinical practice and the optimal criteria for patient selection remain unclear. A family history of kidney disease emerges as one marker associated with a high diagnostic yield of genetic testing. We present 3 cases of adult-onset CKD with underlying monogenic causes exemplifying different modes of inheritance. Case 1 is a 60-year-old male with slowly progressive CKD initially ascribed to hypertension and diabetes despite a family history with several affected first-degree relatives. A pathogenic MUC1 variant was found, and thus we identified the first Danish family of MUC1-associated autosomal dominant tubulointerstitial kidney disease. Case 2 is a 40-year-old female with nephrocalcinosis, nephrolithiasis, and unexplainable hypercalcemia consistent with vitamin D intoxication. The family history indicated autosomal recessive inheritance, and genetic testing revealed 2 pathogenic CYP24A1 variants in compound heterozygous form associated with idiopathic infantile hypercalcemia. Case 3 is a 50-year-old male with microscopic hematuria, proteinuria, and hearing loss. Electron microscopy of renal biopsy showed thin basal membrane syndrome, and the family history indicated X-linked inheritance. A novel missense variant in COL4A5 was identified, suggesting an atypical late-onset form of X-linked Alport syndrome. This case series illustrates the heterogeneous presentations of monogenic kidney disease in adults and emphasizes the importance of family history for initiating genetic testing to identify underlying monogenic causation. Moreover, we discuss the potential impact of genetic diagnostics on patient management and genetic family counseling.

The Hypomorphic Variant p.(Gly624Asp) in <i>COL4A5</i> as a Possible Cause for an Unexpected Severe Phenotype in a Family With X-Linked Alport Syndrome.

<bBackground:</b Alport syndrome (AS) is a progressive kidney disorder leading to end stage renal disease (ESRD). Extrarenal symptoms like hearing loss and ocular changes can be observed. Approximately 85% of the patients carry pathogenic variants in <iCOL4A5</i (X-linked inheritance). The variant c.1871G>A, p.(Gly624Asp) in <iCOL4A5</i is described in the literature as a hypomorphic variant associated with thin basement membrane nephropathy (TBMN). ESRD was only seen rarely at a median age of 50 years and extrarenal manifestations have only been described in single cases. <bCase report and Methods:</b This is a report on a family with X-linked AS. In the female index patient, microscopic hematuria, and proteinuria were observed beginning at the age of 20 years and 41 years, respectively. Microscopic hematuria was also present in the daughter (from 6th month of life), the son (from 22nd month of life), the mother and the maternal grandniece. Proteinuria was observed in the maternal aunt and paternal grandmother. The father of the index patient, a paternal uncle and a second cousin presented with ESRD at the age of 49, 34, and 70 years of life, respectively. Extrarenal manifestations were absent in the whole family. In the index patient, her children and her mother molecular diagnostics were performed using Sanger and exome sequencing. <bResults:</b In all examined family members the variant c.1871G>A, p.(Gly624Asp) in <iCOL4A5</i was identified. With the exception of the index patient, who was homozygous for this variant, all family members carried the variant heterozygously, or hemizygously. A different or additional monogenic hereditary nephropathy could not be detected by exome sequencing of the index patient. <bDiscussion:</b This is the first report of a patient with the variant p.(Gly624Asp) in <iCOL4A5</i in a homozygous state. The variant was previously reported as a mild variant requiring dialysis in less than 10%. The family presented, however, with a more severe clinical course. We therefore suggest to question the term "hypomorphic" in the context of the variant p.(Gly624Asp) although molecular diagnostics could not be done in all affected family members.

Novel mutation in the <i>SALL1</i> gene in a four-generation Chinese family with uraemia: A case report.

Approximately 10% of adults and nearly all children who receive renal replacement therapy have inherited risk factors or are related to genetic factors. In the past, due to the limitations of detection technology and the nonspecific manifestations of uraemia, the etiological diagnosis is unclear. In addition to common monogenic diseases and complex disorders, advanced testing techniques have led to the recognition of more hereditary renal diseases. Here, we report a four-generation Chinese family in which four individuals had a novel <iSALL1</i mutation and presented with uraemia or abnormal urine tests. A 32-year-old man presented with end-stage renal disease with a 4-year history of dialysis. His father and paternal aunt both had a history of unexplained renal failure with haemodialysis, and his 10-year-old daughter presented with proteinuria. The patient had multiple congenital abnormalities, including bilateral overlapping toes, unilateral dysplastic external ears, and sensorineural hearing loss. His family members also presented with similar defects. Genetic testing revealed that the proband carried a novel heterozygous shift mutation in <iSALL1_</iexon 2 (c.3437delG), and Sanger sequencing confirmed the same mutation in all affected family members. We report a novel <iSALL1</i exon 2 (c.3437delG) mutation and clinical syndrome with kidney disease, bilateral overlapping toes, unilateral dysplastic external ears, and sensorineural hearing loss in a four-generation Chinese family.

Mesoamerican nephropathy

Suspected disease: Estimated GFR (eGFR) < 60 ml/min/1.73m2 Absence of diabetes, hypertension, autoimmune disease, glomerular disease, congenital kidney disease, obstructive kidney disease as a clear cause of kidney disease (these comorbidities may be present but cannot account for disease development) Residing in a hotspot region Proteinuria < 2g/24h or 2g/g urine creatinine Likely disease: All of the above, plus eGFR < 60 ml/min/1.73m2 on 3 month or longer repeat measurement Relative hypokalemia and/or hyperuricemia Kidney ultrasound with loss of corticomedullary differentiation or bilateral small kidney size, without cystic disease or large stone burden Kidney biopsy showing primary tubulointerstitial disease without alternative cause of kidney disease in evidence

Thin basement membrane disease

Some individuals with TBMD are thought to be carriers for genes that cause Alport syndrome. Diagnosis Thin basement membrane disease must be differentiated from the other two common causes of glomerular hematuria, IgA nephropathy and Alport syndrome. The history and presentation are helpful in this regard: In Alport syndrome, there is often a family history of kidney failure, which may be associated with hearing impairment. Also, males tend to be more affected as Alport syndrome is X-linked in most cases. In IgA nephropathy, episodes of frank hematuria are more common, and a family history is less common.

List of MeSH codes (C12)

– kidney diseases – aids-associated nephropathy – anuria – diabetes insipidus – diabetes insipidus, nephrogenic – diabetes insipidus, neurogenic – wolfram syndrome – diabetic nephropathies – fanconi syndrome – hepatorenal syndrome – hydronephrosis – hyperoxaluria, primary – hypertension, renal – hypertension, renovascular – kidney calculi – kidney cortex necrosis – kidney diseases, cystic – medullary sponge kidney – multicystic dysplastic kidney – polycystic kidney diseases – polycystic kidney, autosomal dominant – polycystic kidney, autosomal recessive – kidney neoplasms – carcinoma, renal cell – wilms tumor – denys-drash syndrome – wagr syndrome – nephroma, mesoblastic – kidney papillary necrosis – nephritis – glomerulonephritis – anti-glomerular basement membrane disease – goodpasture syndrome – glomerulonephritis, iga – glomerulonephritis, membranoproliferative – glomerulonephritis, membranous

IgA nephropathy

will show red blood cells, usually as red cell urinary casts. Proteinuria, usually less than 2 grams per day, also may be present. Other renal causes of isolated hematuria include thin basement membrane disease and Alport syndrome, the latter being a hereditary disease associated with hearing impairment and eye problems.

Long-term outcome among females with Alport syndrome from a single pediatric center.

Alport syndrome (AS) is a multisystem condition which can result in progressive kidney disease, hearing loss, and ocular changes. X-linked inheritance is observed in 85% of affected individuals. As a result, most prior studies have focused on males. Girls with AS can also be symptomatic although historically thought to have few clinical manifestations in childhood. The objective of the study was to describe the clinical presentation and course of females with AS. A single-center retrospective study of all young females with AS between January 1, 1987, and May 20, 2019. Subjects were identified using ICD-9/10 diagnosis codes for AS, familial hematuria, or nephritis. Clinical data were extracted by retrospective chart review. Thirty-six female patients were included in the analysis. Mean age at presentation was 5.58 ± 3.0 years, and mean follow-up was 5.9 ± 3.9 years. Twenty-nine patients (80%) had a family history of AS. At end of the follow-up period, gross hematuria was observed in 15 patients (42%), 20 (56%) developed proteinuria, and 2 (6.7%) had an estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73m<sup2</sup with one patient developing stage 5 chronic kidney disease. Four of the twenty-seven (14.8%) who underwent audiologic testing had an abnormal exam. Known family histories of AS or gross hematuria were the most common reasons for the initial presentation in our cohort. Development of proteinuria, eGFR < 90 ml/min/1.73m<sup2</sup, and abnormal audiology exam are not exceptional findings, suggesting that close monitoring of young females into adulthood is warranted.

Barakat syndrome

Barakat syndrome, is a rare disease characterized by hypoparathyroidism, sensorineural deafness and renal disease, and hence also known as HDR syndrome. It was first described by Amin J. Barakat et al. in 1977. Presentation It is a genetic developmental disorder with clinical diversity characterized by hypoparathyroidism, sensorineural deafness and renal disease. Affected people usually present with hypocalcaemia, tetany, or afebrile convulsions at any age. Hearing loss is usually bilateral and may range from mild to profound impairment. Renal disease includes nephrotic syndrome, cystic kidney, renal dysplasia, hypoplasia or aplasia, pelvicalyceal deformity, vesicoureteral reflux, chronic kidney disease, hematuria, proteinuria and renal scarring. Other reported features include: intellectual disability, polycystic ovaries, particular distinct facial characteristics, ischaemic stroke and retinitis pigmentosa.

Phenotypic heterogeneity in females with X-linked Alport syndrome.

X-linked Alport syndrome (AS) is a monogenic inherited disorder of type IV collagen, a structural protein in the kidney and cochlea. Males typically exhibit a severe phenotype with end-stage renal disease (ESRD) and/or deafness by early adulthood. Because of the presence of two X chromosomes, females often have a less severe phenotype and hence the diagnosis of AS is often not considered. Herein, we present a case of an adolescent girl with proteinuria and hematuria in the setting of a strong family history of AL. The mother and maternal aunt of the proband had both presented with dipstick positive hematuria and proteinuria at age 8 years. These girls were not evaluated by nephrology until mid-adolescence when they had worsening creatinine levels. Kidney biopsy in the younger sister demonstrated segmental glomerulosclerosis with segmental thinning and lamination of the glomerular basement membrane, consistent with AS. Kidney biopsy in the older sister was performed just prior to the need for renal replacement therapy and showed only global glomerulosclerosis. Both sisters were transplanted by the age of 20 years. Their mother subsequently developed ESRD at age 53 years. With the advent of genetic testing, the proband and her family were brought in for evaluation. It had been assumed this family of AS had autosomal dominant transmission, however, genetic testing of the proband was positive for a splice site mutation of COL4A5 located on the X-chromosome. Sequencing of genes COL4A3, COL4A4, and COL4A6 were negative for mutation. The current case report demonstrates the importance of considering skewed X-inactivation in females who exhibit signs or symptoms of Xlinked disorders.

Alport syndrome

Gene therapy has been frequently discussed, but delivering it to the podocytes in the glomerulus that normally produce the type IV collagen in the glomerular basement membrane is challenging. Hearing loss It is not known whether ACE inhibitors or other treatments affect hearing loss. For those with classic Alport syndrome, hearing aids are often required in teenage or young adult years. Prognosis Studies of the life expectancy of patients with Alport syndrome are rare, but one 2012 study found that Alport patients receiving renal replacement therapy (dialysis or kidney transplantation) exhibited, on average, better survival compared with matched controls who had other renal diseases (and who also received renal replacement therapy). See also AMMECR1 Samoyed hereditary glomerulopathy, a disease shown to be a model for Alport syndrome. Fechtner syndrome Thin basement membrane disease References External links GeneReview/NIH/UW entry on Alport syndrome

Assessment of kidney function

The severity of chronic kidney disease (CKD) is described by six stages; the most severe three are defined by the MDRD-eGFR value, and first three also depend on whether there is other evidence of kidney disease (e.g., proteinuria): 0) Normal kidney function – GFR above 90 (mL/min)/(1.73 m2) and no proteinuria 1) CKD1 – GFR above 90 (mL/min)/(1.73 m2) with evidence of kidney damage 2) CKD2 (mild) – GFR of 60 to 89 (mL/min)/(1.73 m2) with evidence of kidney damage 3) CKD3 (moderate) – GFR of 30 to 59 (mL/min)/(1.73 m2) 4) CKD4 (severe) – GFR of 15 to 29 (mL/min)/(1.73 m2) 5) CKD5 kidney failure – GFR less than 15 (mL/min)/(1.73 m2) Some people add CKD5D for those stage 5 patients requiring dialysis; many patients in CKD5 are not yet on dialysis. Note: others add a "T" to patients who have had a transplant regardless of stage.

Glomerular filtration rate

The severity of chronic kidney disease (CKD) is described by six stages; the most severe three are defined by the MDRD-eGFR value, and first three also depend on whether there is other evidence of kidney disease (e.g., proteinuria): 0) Normal kidney function – GFR above 90 mL/min/1.73 m2 and no proteinuria 1) CKD1 – GFR above 90 mL/min/1.73 m2 with evidence of kidney damage 2) CKD2 (mild) – GFR of 60 to 89 mL/min/1.73 m2 with evidence of kidney damage 3) CKD3 (moderate) – GFR of 30 to 59 mL/min/1.73 m2 4) CKD4 (severe) – GFR of 15 to 29 mL/min/1.73 m2 5) CKD5 kidney failure – GFR less than 15 mL/min/1.73 m2 Some people add CKD5D for those stage 5 patients requiring dialysis; many patients in CKD5 are not yet on dialysis. Note: others add a "T" to patients who have had a transplant regardless of stage.

The renal allograft donor with isolated microhematuria.

Recently, there has been extensive debate about extending the criteria for accepting living donors to include the presence of mild renal abnormalities such as isolated microhematuria. Hematuria defined as the detection of greater than five red blood cells per high power field can be associated with abnormalities throughout the urinary tract. Detection of casts or dysmorphic red blood cells in the urine sediment with or without proteinuria could indicate underlying intrinsic renal disease. Anatomic causes, such as stones and tumors, should be excluded; cystoscopy may be indicated to exclude bladder pathology. Obviously, urinary tract infection, uncontrolled hypertension and latent diabetes mellitus must be excluded. Microscopic hematuria could be associated with mesangial IgA deposits; as 10% of first-degree relatives of patients with IgA glomerulonephritis suffer from microhematuria and/or proteinuria that may require consideration of renal biopsy. Microhematuria could also be associated with other known hereditary renal diseases such as C3 deposits disease, IgM nephropathy, autosomal dominant polycystic kidney disease, Alport's syndrome or thin basement membrane disease. In conclusion, careful assessment of isolated microhematuria, in the context of living kidney donation, is mandatory as results may reveal occult renal disease that may contraindicate kidney donation.

[Familial hematuria and Alport's syndrome].

In their review the authors discuss the history of Alport's syndrome, its nomenclature, incidence, genetics, clinical diagnosis. The authors emphasize electron microscopic findings and criteria of the diagnosis (haematuria or renal failure in the family, progressive nervous deafness, typical changes of the basal glomerular membrane (GBM) and ophtalmological findings of lenticonus or perimacular spots. Familial haematuria (FH) is according to the authors defined as haematuria in several members of the family. Based on data in the literature and the authors' experience, the authors discuss the differential diagnosis of FH where Alport's syndrome is relatively rare. A far more frequent unit is benign familial haematuria characterized morphologically as isolated thinning of the GBM. In some cases these patients are threatened by iatrogenic damage from unnecessary and invasive diagnostic method. The finding of thinned GBM and normal renal function in the parents and grandparents suggest a favourable prognosis also in child patients. Cases of familial glomerulonephritis or idiopathic syndrome with glomerulosclerosis or familial IgA nephropathies are relatively rare. Familial haematuria is are relatively rare. Familial haematuria is relatively frequent (according to the authors 20% of all obscure haematurias) and their diagnosis is based on systematic examination of the urine in other members of the patient's family who also suffer from haematuria.

Familial thin basement membrane nephropathy in children with asymptomatic microhematuria.

A review of 130 children with persistent microhematuria showed that the most common abnormality was a form of hereditary nephritis for wich we propose the term 'familial thin basement membrane nephropathy' (FTBMN). This lesion is not as severe as that of Alport's syndrome but carries a guarded prognosis. Family histories, urinalyses and audiograms systematically done on parents and other relatives show that FTBMN may be present in as many as 39% of children with persistent microhematuria and that careful family studies identify children likely to have this lesion.

[Prevalence of kidney disease in asymptomatic children with family history of renal replacement therapy].

Having a first- or second-degree relative with chronic kidney disease (CKD) has been reported as a risk factor for CKD development. The aim of the study was to determine the prevalence of CKD in children with a first- or second-degree relative undergoing renal replacement therapy (hemodialysis or renal transplant). A screening study was performed in asymptomatic children with a family history of CKD in a first- or second-degree relative undergoing renal replacement therapy. Informed consent was obtained in all cases. A clinical examination was performed. Blood and urine samples were obtained for serum creatinine, serum electrolytes, urinalysis, and microalbumin/creatinine ratio. There were 45 subjects included with a median age of 9.6 years; 24 (53%) were male. Urinary abnormality/CKD was observed in 11 subjects (24.4%). The most common urinary abnormalities were hematuria (6/11) and microalbuminuria (4/11). Stage 2 CKD was found in seven subjects and four subjects with stage 1 CKD. The study of families of patients undergoing renal replacement therapy is useful to identify children in early stages of kidney disease.

Samoyed hereditary glomerulopathy

Description SHG is caused by a nonsense mutation in codon 1027 of the COL4A5 gene on the X chromosome (glycine to stop codon), which is similar to Alport syndrome in humans. The disease is simply inherited, X-linked dominant, with males generally having more severe symptoms than females. Clinically, from the age of three to four months, proteinuria in both sexes is seen. In dogs older than this, kidney failure in combination with more or less pronounced hearing loss occurs swiftly, and death at the age of 8 to 15 months is expected. In heterozygous females, whereby only one of the two X chromosomes carry the mutation, the disease develops slowly.

[Steroid-responsive nephrotic syndrome in IgA nephropathy].

A 46-year-old male, smoker of half a packet a day and an alcohol intake of 80 grams a day, with an unremarkable medical history, was referred to our service in the year 1988 for a study of nephrotic syndrome. He presented normal renal function, without either microhematuria nor hypertension. In blood analysis an albuminemia of 10 g/l and proteinuria of 22 g/d was observed. A first renal biopsy was carried out which indicated minimal change disease. Steroid treatment was started, as a result the nephrotic syndrome disappeared and the blood analysis normalized. Later he had 4 new outbreaks, all of them steroid-responsive. In 1992 a second renal biopsy was performed after the fourth outbreak and the presence of mild renal failure, that this time indicated a IgA nephropathy. Steroid treatment was tried again, and this time cyclophosphamide was added to try to reduce steroid doses. This result in normalization of renal function and decrease of proteinuria to 2 g/d. The patient remained stable until 1996 when the fifth outbreak occurred, again with mild renal failure and proteinuria in nephrotic range. Therefore a third renal biopsy was performed, that confirmed the presence of IgA nephropathy, but now with signs of histological progression of the disease. Following this, he presented five outbreaks in 3 years, all of them steroid-responsive, with decrease of proteinuria although without renal function normalization. In the year 2000, at his tenth outbreak of nephrotic syndrome it was decided to add cyclosporine to the steroid treatment, achieving the stability of the patient, without further outbreaks until now, with proteinuria of 1.6 g/d and C. creat. 59 ml/min.

[Epidemiological study in 4 family units with Alport's syndrome].

At the Nephrology Department of the Hospital Infantil de Mexico, four cases of Alport's syndrome. with no relation among themselves, were studied between, June 1978 and November 1979. The diagnosis was based on the presence in the patients, of proteinuria and/or hematuria and in some of the relatives, a history of renal disease, deafness and a variable degree of renal failure; at the renal biopsy examined with electronic microscopy, there were findings compatible with Alport's disease in all four cases. Field studied were carried in the largest possible number of relatives for each family group the clinical viewpoint including measurement of blood pressure, examination of urine with reactive stripes to detect proteinuria and hematuria and audiologic examination. In the group, 130 subjects were studied out of a total of 237; 37% were found affected; 21% complaining of deafness; four female cases (19%) had not reach an uremic condition. From the second group 36 subjects were studied out of 109 members. Fifty per cent were found affected. Three cases had reached an uremic state (15%). Out of the third group with a total of 74 members, 34 cases were studied and 62% were found affected. Two female cases (12%) were complaining of uremia. The third group comprised 60 members and 19 of them were studied finding 13% affected with 2 cases of uremia. There were cases exclusively with renal or auditive involvement or both, at the same time. In our casuistics, most of the cases affected of the kidney or of the auditive apparatus were female patients; likewise, the most severely ill were females. Out of the 106 patients affected of the kidney, there were 11 with uremia and 8 were females. It was noticed that both males and females who were affected, had children of either sex with the same degree of affection, the same as other children with no changes at all; therefore, it is concluded that transmission is by dominant autosomal heredity.

Nephrotic-range proteinuria in an infant with thin basement membrane nephropathy.

Thin basement membrane nephropathy (TBMN) with heterozygous COL4A3/COL4A4 mutations is considered to be a cause of benign familial hematuria. The disease has been believed to have excellent prognosis and TBMN in early childhood is rarely associated with nephrotic-range proteinuria. Furthermore, the presence of proteinuria in patients with TBMN is associated with autosomal-dominant Alport syndrome, which has poorer prognosis in later life. We present an infant case of nephrotic-range proteinuria associated with TBMN caused by heterozygous COL4A4 mutation. A previously healthy 3-year-old boy developed microhematuria and nephrotic-range proteinuria. Renal pathology simply revealed thinning of the glomerular basement membrane (GBM) and mutational analysis revealed a novel heterozygous mutation in COL4A4. He was treated with lisinopril for 1.5 years, which resolved his proteinuria and hematuria. At the most recent follow-up at 6.5 years of age, urinalysis and kidney function were completely normal, without requiring medication. However, transient but repeated moderate to nephrotic-range proteinuria and microscopic hematuria occurred in association with other illnesses. This case highlights the spectrum of phenotypes that may be apparent in an infant with TBMN. Thinning of the GBM can cause transient nephrotic-range proteinuria, particularly in the early stages of TBMN.

Living related kidney transplantation in a patient with autosomal-recessive Alport syndrome.

We discuss a patient with Alport syndrome who received a renal transplant from a donor with thin basement membrane disease. A 30-year-old woman, diagnosed with Alport syndrome on the basis of sensorineural hearing loss, characteristic renal biopsy findings and a family history of microhaematuria, entered chronic haemodialysis therapy. She then received a renal transplant donated from her father, who had sensorineural hearing loss and persistent microhaematuria. On the day of renal transplantation, a 1-h graft biopsy after reperfusion showed thin basement membrane disease. We re-tested the patient's native kidney biopsy specimen by immunohistochemical staining using alpha-chain-specific collagen type IV monoclonal antibodies. There was no expression of collagen type IV alpha3-, alpha4- and alpha5-chain on glomerular basement membrane, but positive staining of alpha5-chain on Bowman's capsular basement membrane was noted. A diagnosis of autosomal-recessive Alport syndrome was made. We concluded that this family might display different phenotypic expressions of the same genotype: one suffered end-stage renal disease and the other thin basement membrane disease.

Proteinuria

Proteinuria may be a feature of the following conditions: Nephrotic syndromes (i.e. intrinsic kidney failure) Pre-eclampsia Eclampsia Toxic lesions of kidneys Amyloidosis Collagen vascular diseases (e.g. systemic lupus erythematosus) Dehydration Glomerular diseases, such as membranous glomerulonephritis, focal segmental glomerulonephritis, minimal change disease (lipoid nephrosis) Strenuous exercise Stress Benign orthostatic (postural) proteinuria Focal segmental glomerulosclerosis (FSGS) IgA nephropathy (i.e. Berger's disease) IgM nephropathy Membranoproliferative glomerulonephritis Membranous nephropathy Minimal change disease Sarcoidosis Alport syndrome Diabetes mellitus (diabetic nephropathy) Drugs (e.g. NSAIDs, nicotine, penicillamine, lithium carbonate, gold and other heavy metals, ACE inhibitors, antibiotics, or opiates (especially heroin) Fabry disease Infections (e.g. HIV, syphilis, hepatitis, poststreptococcal infection, urinary schistosomiasis)

Two families with Alport's syndrome.

Alport's syndrome is a hereditary disease striking cochlea, eye and kidney. The diseased women usually have a nonlethal degree of the kidney disease, but the prognosis for the men is worse. They often die from renal failure before the age of 35. Most cases of hearing loss occurs in men. The hearing loss is progressive after the age of 10. Audiological tests are characteristic for a cochlear lesion. The debut of the disease usually appears in the post natal period giving microscopic haematuria. It can, however, occur later with haematuria and proteinuria. The hearing loss may be the first symptom, which is an observandum to otologists. Two families with Alport's syndrome are described. The patients have been examined concerning kidney disease, audiological and vestibular pathology. The hereditary pattern is described.

An overlap of Alport syndrome and rheumatoid arthritis in a patient and literature review.

Alport syndrome is a rare genetic kidney disease, and rheumatoid arthritis as a common autoimmune disease also causes renal lesions in addition to arthritis. The overlap of them has rarely been reported. A 44-year-old man had a history of multi-joint swelling and pain for more than half a year. His laboratory data with double positive for rheumatoid factor and anticitrullinated protein antibodies further supported the diagnosis of early rheumatoid arthritis. His previous medical history including progressive hearing loss for several years and microhematuria for one year attracted our attention. Renal biopsy showed thin basement membrane nephropathy and lymphocytes infiltration of interstitium. To make a precise diagnosis, targeted Next Generation Sequencing (NGS) of an inherited renal disease panel including Alport syndrome genes was performed, which revealed the missense mutation in COL4A5 (c.1351 T > C, p.Cys451Arg). Further in silico analyses predicted that the p. Cys451Arg mutation is functionally "damaging", so the diagnosis of Alport syndrome was finally proved. The patient has been receiving the treatment of total glucosides of paeony and leflunomide for rheumatoid arthritis, and Cozaar 50 mg for the protection of kidney so far. During the 10-months follow-up, swelling and tenderness of the joints in this patient had been generally relieved, with no obvious improvement in microhematuria and a slight increase in proteinuria. we reported an adult man with the coexistence of rheumatoid arthritis and Alport syndrome with the missense mutation in COL4A5 (c.1351 T > C, p.Cys451Arg). Whether the overlap of them is occasional or has a common pathophysiological mechanism is still unclear.

Alport's syndrome. A report of three Swedish families.

Three families with hereditary nephritis of Alport's type have been studied with particular emphasis on the occurrence of symptoms and signs in different sexes and age groups. Part of the material was tested for impaired hearing or eye anomalies which may be the sole manifestation of Alport's yndrome. The youngest patients were 3-4 years of age, and the proportion of diseases individuals increased with age. In two of the families about half of the investigated males or females were affected whereas in the third family all but one of 16 investigated individuals were affected. In this last family the kidney disease was exceptionally severe, but no differences in the histopathology of the kidney lesions were seen between the families. In all the families renal symptoms progressed more rapidly in males than in females. Affected as well as unaffected sons and daughters were born to healthy as well as to diseased mothers. In contrast, healthy fathers produced only unaffected children. Diseased fathers produced only daughters, two-thirds of whom were affected. It is concluded that Alport's syndrome in these three families most probably is transmitted by autosomal dominant inheritance with variations in expression and penetrance.


Calcium gluconate has no effect on blood potassium levels (therefore options 1, 2 and 3 are ruled out). Its function is to decrease the excitability of cardiac myocytes to decrease the likelihood of developing heart rhythm disorders.

Calcium gluconate has no effect on blood potassium levels (therefore [HIDDEN]). Its function is to decrease the excitability of cardiac myocytes to decrease the likelihood of developing heart rhythm disorders.

A 5-year-old boy diagnosed with chronic renal failure. He comes to the emergency department with vomiting, malaise, and palpitations. An electrocardiogram was performed with T-wave elevation and blood tests showed potassium levels of 5.9 mEq/L. Immediate administration of calcium gluconate is decided. What is the purpose of this treatment?

Encourage the displacement of potassium from the plasma space to the intracellular space.

Chelate circulating potassium to favor its hepatic elimination.

Chelate circulating potassium to favor its renal elimination.

Antagonize the action of potassium on the myocardial cell membrane.

[Life threatening hyperkalemia: the value of the electrocardiogram].

In two men, aged 19 and 64, with chronic renal insufficiency and subacute symptoms of malaise and weakness of the leg muscles, broad QRS complexes were seen in the ECG. The younger patient developed an asystole and resuscitation was unsuccessful. His blood potassium level was found to be 8.3 mmol/l. The older patient recovered after administration of calcium gluconate. His blood potassium level was found to be 8.5 mmol/l. An 80-year-old woman who was taking various drugs because of heart failure also complained of muscle weakness. Her blood potassium level was 7.2 mmol/l and her ECG showed narrow complexes. She recovered without calcium gluconate after a change in medication. Hyperkalemia is a potentially life-threatening electrolyte disorder that may require immediate treatment. The changes in the ECG, especially widening of the QRS complexes, are the most important clues to the severity of the hyperkalemia. A treatment protocol based on ECG changes may reduce the mortality in these patients.

[Atrial arrest and intraventricular conduction disorders due to accidental hyperkalemia during kidney transplantation].

Besides anemia, coagulopathies, and hypertension, electrolyte disturbances are among the most significant features of end-stage renal disease. Although plasma potassium represents only 1.5%-2% of the whole-body content, hyperkalemia has definite effects on cardiac pacemaker cells and myocardial conduction. The typical ECG findings and therapeutic management will be discussed. Case report. A 64-year-old man with chronic renal failure due to phenacetin abuse was scheduled for transplantation of a 41-h-old cadaver kidney. The preoperative laboratory check revealed BUN 51 mg% and creatinine 11.5 mg%; serum sodium and potassium were within normal limits (sodium 141 mmol/l, potassium 5.11 mmol/l). A central-venous blood gas sample after induction of anesthesia and intubation revealed pH of 7.32, pCO2 43 mmHg, HCO3 22.1 mmol/l, base excess - 3.4 mmol/l, and venous oxygen saturation 84%. Plasma potassium (5.22 mmol/l) was within the normal range. As an endarterectomy of the left common and external iliac arteries had to be performed, the arterial cross-clamping time was longer than normal (73 min). After declamping an ECG pattern (modified V5 lead) typical of hyperkalemia (atrial arrest, idioventricular rhythm, right bundle-branch block-like QRS, AV dissociation, AV block I) was observed. Plasma potassium had increased to 6.77 mmol/l (+1.55 mmol/l). Immediate treatment was started with a bolus injection of 20 ml 10% calcium gluconate, rapid infusion of 200 ml 8.4% sodium bicarbonate, and glucose-insulin infusion (glucose 33 1/3%, 15 U regular insulin). After 25 min sinus rhythm was restored and potassium levels decreased to normal. Despite the observed ECG changes the cardiovascular status remained stable.(ABSTRACT TRUNCATED AT 250 WORDS)

[Safe treatment of acute hyperkalemia : The 1:4 and other principles].

Acute hyperkalemia is a dangerous electrolyte disorder, which must be treated immediately. It can lead to cardiac arrhythmia and death due to alterations in cell membrane potentials. The resulting alterations in the electrocardiogram (ECG) are multifarious and need to be rapidly recognized. Treatment consists of various stages. In addition to membrane stabilization, which is always necessary, potassium must be displaced into the intracellular space and then eliminated from the body. A commonly applied method for displacement of potassium into the intracellular space involves the administration of insulin-glucose mixtures, which is associated with many complications. In the clinical routine many prescription variations are applied, which do not always appear to be ideal with respect to the individual risk-benefit ratio. A practically useful and easily memorized insulin-glucose mixture has a relationship of 1IU insulin to 4g glucose. The therapeutic elimination from the body is carried out using an enhanced diuresis or the utilization of renal replacement procedures. Special attention must be paid to the continous monitoring of potassium and blood sugar levels. After overcoming the acute situation, attention must be paid to treatment of the underlying disorder and if necessary to readjustment of the long-term medication of the patient.

Potassium binder

Potassium, the most abundant intracellular cation, is essential for life. An adequate gradient of potassium across the cell membrane is necessary in order to enable excitability of cell membranes. This is particularly important for nerve and muscle function. In humans, mainly the kidneys are responsible for the regulation of serum potassium levels by excreting excess potassium via the urine. As kidney failure progresses, with a consequent decline of excretory function, potassium is likely to accumulate with probable harmful effects on the cellular membrane potential and cardiac arrhythmias as the primary symptom. If the physiological potassium blood level of between 3.8 mmol/L and 5.2 mmol/L is exceeded, hyperkalaemia is diagnosed. The mainstay of the treatment for chronic kidney disease patients is potassium removal through the dialysis procedure. However, dietary restrictions and pharmaceutical therapy with potassium binders are important complementary treatment options.

Potassium

Homeostasis Potassium homeostasis denotes the maintenance of the total body potassium content, plasma potassium level, and the ratio of the intracellular to extracellular potassium concentrations within narrow limits, in the face of pulsatile intake (meals), obligatory renal excretion, and shifts between intracellular and extracellular compartments. Plasma levels Plasma potassium is normally kept at 3.5 to 5.5 millimoles (mmol) [or milliequivalents (mEq)] per liter by multiple mechanisms. Levels outside this range are associated with an increasing rate of death from multiple causes, and some cardiac, kidney, and lung diseases progress more rapidly if serum potassium levels are not maintained within the normal range. An average meal of 40–50mmol presents the body with more potassium than is present in all plasma (20–25mmol). However, this surge causes the plasma potassium to rise only 10% at most as a result of prompt and efficient clearance by both renal and extra-renal mechanisms.

Hs and Ts

A common presentation of hyperkalemia is in the patient with end-stage renal disease who has missed a dialysis appointment and presents with weakness, nausea, and broad QRS complexes on the electrocardiogram. (Note however that patients with chronic kidney disease are often more tolerant of high potassium levels as their body often adapts to it.) Several medications, for example the antibiotic trimethoprim/sulfamethoxazole or an ACE inhibitor, can also lead to the development of significant hyperkalemia. The electrocardiogram will show tall, peaked T waves (often larger than the R wave) or can degenerate into a sine wave as the QRS complex widens. Immediate initial therapy is the administration of calcium, either as calcium gluconate or calcium chloride. This stabilizes the electrochemical potential of cardiac myocytes, thereby preventing the development of fatal arrhythmias. This is, however, only a temporizing measure. Other temporizing measures may include nebulized salbutamol,

Electrolyte imbalance

Hypokalemia The most common electrolyte disturbance, hypokalemia means that the concentration of potassium is <3.5 mEq/L. It often occurs concurrently with low magnesium levels. Causes Low potassium is caused by increased excretion of potassium, decreased consumption of potassium rich foods, movement of potassium into the cells, or certain endocrine diseases. Excretion is the most common cause of hypokalemia and can be caused by diuretic use, metabolic acidosis, diabetic ketoacidosis, hyperaldosteronism, and renal tubular acidosis. Potassium can also be lost through vomiting and diarrhea. Symptoms Hypokalemia is often asymptomatic, and symptoms may not appear until potassium concentration is <2.5 mEq/L. Typical symptoms consist of muscle weakness and cramping. Low potassium can also cause cardiac arrythmias.

Clinical potassium problems.

Alterations in serum potassium are common in many diseases. In a series of 390 determinations of serum potassium, the levels found were low in 24 per cent and high in 2.6 per cent. The major causes of low serum potassium are (1) decreased potassium intake due to intravenous feedings which do not contain potassium; (2) increased loss of potassium in the urine due to accelerated tissue breakdown, or renal lesions; (3) loss from the gastrointestinal tract due to diarrhea, or fistulae, and (4) shift between serum and cells, due to metabolic causes, drugs or changes in pH. The major cause of high serum potassium is uremia with renal retention.Clinical symptoms and signs of low body potassium include muscle weakness and paralysis, which may lead to death in respiratory failure if not corrected, tachycardia, gallop rhythm, dilatation of the heart. The electrocardiogram shows inverted, low amplitude, or isoelectric T waves and a prolonged QT interval. Potassium chloride orally, subcutaneously or intravenously is recommended for use in the treatment of potassium deficits. It should not be used in the presence of oliguria or anuria or dehydration. The amounts of potassium necessary to correct deficits vary widely and cannot be predicted from the serum level. Special reference is made to the prevention and therapy of potassium deficits in diabetic acidosis. High serum potassium levels are difficult to correct. Suggested measures are administration of glucose, insulin or calcium, gastric or peritoneal lavage or use of the artificial kidney.

EMS Confined Space Care -- Issues of Concern -- Crush Injury and Crush Syndrome

Several electrolyte abnormalities may be present. Hypocalcemia should only be treated if the patient is symptomatic since the patient may later develop hypercalcemia. Start with 10 mL of intravenous calcium gluconate 10% or 5 mL of intravenous calcium chloride 10% over 2 minutes.  Hyperkalemia should be monitored and treated based on the potassium level and electrocardiographic changes.   The ECG may not change in some situations where the potassium level is dangerously elevated.  If there are severe or life-threatening electrocardiographic changes or arrhythmias such as the widening of the QRS to third-degree heart block or pulseless electrical activity, the intravenous calcium gluconate or chloride should be given immediately. It may be necessary to give several doses every 10 minutes to achieve the cardioprotective effects of calcium. If the patient is acidotic then sodium bicarbonate 1 meq/kg should be given immediately IV over several minutes.  To drive the potassium into the cells, 10 units of intravenous insulin, together with 1 to 2 ampules of D50, should be given.   The Beta agonist effect of albuterol inhalation treatments can also help transiently decrease potassium levels.  Kaexylate with sorbitol can be given orally at 25 to 50 gm, or it may be given as a retention enema.  Patients with life-threatening hyperkalemia need the potassium removed from their system.  The medications and treatments are temporizing measures to provide time for excretion of removal of potassium from the body.  The patient may require emergent dialysis.  Critiques of recent disaster responses were that there was an insufficient number of dialysis machines to treat those with renal failure secondary to crush injuries.  Blood products should be given as necessary and when indicated.

Treatment and pathogenesis of acute hyperkalemia.

This article focuses on the pathogenesis, clinical manifestations, and various treatment modalities for acute hyperkalemia and presents a systematic approach to selecting a treatment strategy. Hyperkalemia, a life-threatening condition caused by extracellular potassium shift or decreased renal potassium excretion, usually presents with non-specific symptoms. Early recognition of moderate to severe hyperkalemia is vital in preventing fatal cardiac arrhythmias and muscle paralysis. Management of hyperkalemia includes the elimination of reversible causes (diet, medications), rapidly acting therapies that shift potassium into cells and block the cardiac membrane effects of hyperkalemia, and measures to facilitate removal of potassium from the body (saline diuresis, oral binding resins, and hemodialysis). Hyperkalemia with potassium level more than 6.5 mEq/L or EKG changes is a medical emergency and should be treated accordingly. Treatment should be started with calcium gluconate to stabilize cardiomyocyte membranes, followed by insulin injection, and b-agonists administration. Hemodialysis remains the most reliable method to remove potassium from the body and should be used in cases refractory to medical treatment. Prompt detection and proper treatment are crucial in preventing lethal outcomes.

Prerenal Kidney Failure -- Treatment / Management

Due to the risk of life-threatening cardiac arrhythmias, severe hyperkalemia (plasma potassium of more than 6.5 mmol/l) is considered a medical emergency. If the serum potassium is more than 6.5 mmol/l or if any ECG changes (tall peaked T waves, shortened QT interval, prolonged PR interval, wide QRS complex) are present, the treatment of hyperkalemia should be promptly started. By stabilizing the myocardium within a few minutes of infusion, calcium counters the effects of hyperkalemia and produces a more normal ECG trace without affecting serum potassium. If P wave or QRS changes are present, its administration should not be delayed. 10 to 20 ml of 10% calcium gluconate or calcium chloride is given in bolus form intravenously over two to five minutes. [16] Insulin increases intracellular potassium uptake. To prevent hypoglycemia, glucose is added to insulin bolus. Ten units of fast-acting soluble insulin are added to 50 ml of 50% dextrose and given in infusion form intravenously over 10 to 20 minutes. A reduction in potassium level is seen after 20 to 30 minutes. [17]

Sustained-release potassium chloride overdose.

Although ingestion of sustained-release potassium supplements can cause life-threatening hyperkalemia in patients with abnormal renal function, only a few previous reports suggest that this may occur in patients with normal renal function. We report 2 cases of hyperkalemia in patients with normal renal function who developed hyperkalemia after ingesting sustained-release potassium preparations and describe the use of radiography and whole-bowel irrigation in their care. The first patient is a 50-year-old woman who ingested 100 K-Dur tablets (each tablet containing 750 mg KCl or 10 mEq potassium) in a suicide attempt 1 hour prior to presenting to the emergency department. She developed a peak serum potassium level of 9.7 mEq/L and had transient, potentially life-threatening electrocardiographic changes. The second patient was a 17-year-old man who ingested 20 to 30 Klor-Con tablets (each tablet containing 750 mg KCl or 10 mEq potassium) in a suicide attempt 10 hours prior to presentation. Although he developed a peak serum potassium level of 6.1 mEq/L, he had a persistently normal electrocardiogram. In both patients, the tablets were visualized on abdominal radiographs and the gastrointestinal tracts of both were successfully decontaminated using whole-bowel irrigation. Although the sensitivity and specificity are unknown, the abdominal radiograph appears to be useful in detecting sustained-release potassium tablets. Whole-bowel irrigation as a primary method of gastrointestinal decontamination also appears to be effective although its use is not previously reported for sustained-release potassium overdoses.

Calcium gluconate

Calcium gluconate came into medical use in the 1920s. It is on the World Health Organization's List of Essential Medicines. Calcium gluconate is available as a generic medication. Medical uses Low blood calcium 10% calcium gluconate solution (given intravenously) is the form of calcium most widely used in the treatment of low blood calcium. This form of calcium is not as well absorbed as calcium lactate, and it only contains 0.93% (930 mg/dl) calcium ion (defined by 1 g weight solute in 100 ml of solution to make 1% solution w/v). Therefore, if the hypocalcemia is acute and severe, calcium chloride is given instead. High blood potassium Calcium gluconate is used as a cardioprotective agent in people with high blood potassium levels, with one alternative being the use of calcium chloride. It is recommended when the potassium levels are high (>6.5 mmol/l) or when the electrocardiogram (ECG) shows changes due to high blood potassium.

Hyperkalemia

Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0mmol/L (3.5 and 5.0mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasionally when severe it can cause palpitations, muscle pain, muscle weakness, or numbness. Hyperkalemia can cause an abnormal heart rhythm which can result in cardiac arrest and death. Common causes of hyperkalemia include kidney failure, hypoaldosteronism, and rhabdomyolysis. A number of medications can also cause high blood potassium including spironolactone, NSAIDs, and angiotensin converting enzyme inhibitors. The severity is divided into mild (5.5–5.9mmol/L), moderate (6.0–6.4mmol/L), and severe (>6.5mmol/L). High levels can be detected on an electrocardiogram (ECG). Pseudohyperkalemia, due to breakdown of cells during or after taking the blood sample, should be ruled out.

Electrolyte imbalance

Treatment There are three mainstays of treatment of hyperkalemia. These are stabilization of cardiac cells, shift of potassium into the cells, and removal of potassium from the body. Stabilization of cardiac muscle cells is done by administering calcium intravenously. Shift of potassium into the cells is done using both insulin and albuterol inhalers. Excretion of potassium from the body is done using either hemodialysis, loop diuretics, or a resin that causes potassium to be excreted in the fecal matter. Hypokalemia The most common electrolyte disturbance, hypokalemia means that the concentration of potassium is <3.5 mEq/L. It often occurs concurrently with low magnesium levels.

Calcium Gluconate -- Mechanism of Action -- Hyperkalemia

Elevations of extracellular potassium can cause cardiac arrhythmias, which can progress to cardiac arrest and death. The role of calcium gluconate in treating hyperkalemia is to stabilize cardiac cell membranes. Calcium should promptly be administered to any patient presenting with hyperkalemia with EKG changes, indicating a hyperkalemic emergency. Elevated potassium levels destabilize cardiac membranes by increasing the threshold potential of cardiac myocytes. Calcium supplementation decreases the threshold to restore the transmembrane voltage gradient. However, though calcium protects myocytes from potassium, it does not resolve the issue of hyperkalemia, for which other medications are typically administered, such as insulin and dextrose or sodium bicarbonate, which shifts potassium into cells; and sodium polystyrene sulfate, which increases potassium excretion through stool. However, dialysis is the most efficacious means of potassium excretion, particularly in patients with renal disease. [2] [9]

Electrolyte imbalance

Potassium Potassium resides mainly inside the cells of the body, so its concentration in the blood can range anywhere from 3.5 mEq/L to 5 mEq/L. The kidneys are responsible for excreting the majority of potassium from the body. This means their function is crucial for maintaining a proper balance of potassium in the blood stream. Hyperkalemia Hyperkalemia means the concentration of potassium in the blood is too high. This occurs when the concentration of potassium is >5 mEq/L. It can lead to cardiac arrhythmias and even death. As such it is considered to be the most dangerous electrolyte disturbance.

Electrolyte imbalance

Causes Hyperkalemia is typically caused by decreased excretion by the kidneys, shift of potassium to the extracellular space, or increased consumption of potassium rich foods in patients with kidney failure. The most common cause of hyperkalemia is lab error due to potassium released as blood cells from the sample break down. Other common causes are kidney disease, cell death, acidosis, and drugs that affect kidney function. Symptoms Part of the danger of hyperkalemia is that it is often asymptomatic, and only detected during normal lab work done by primary care physicians. As potassium levels get higher, individuals may begin to experience nausea, vomiting, and diarrhea. Patients with severe hyperkalemia, defined by levels above 7 mEq/L, may experience muscle cramps, numbness, tingling, absence of reflexes, and paralysis. Patients may experience arrhythmias that can result in death.

Hypokalemia

In order to correct the pH during alkalosis, these cells will use these mechanisms to reabsorb great amounts of H+, which will concomitantly increase their intracellular concentrations of potassium. This concentration gradient drives potassium to be secreted across the apical surface of the cell into the tubular lumen through potassium channels (this facilitated diffusion occurs in both Type B intercalated cells and Principal cells in the collecting duct).2) Metabolic alkalosis is often present in states of volume depletion, such as vomiting, so potassium is also lost via aldosterone-mediated mechanisms.3) During metabolic alkalosis, the acute rise of plasma HCO3− concentration (caused by vomiting, for example) will exceed the capacity of the renal proximal tubule to reabsorb this anion, and potassium will be excreted as an obligate cation partner to the bicarbonate.

Hyperkalemia

Initial treatment in those with ECG changes is salts, such as calcium gluconate or calcium chloride. Other medications used to rapidly reduce blood potassium levels include insulin with dextrose, salbutamol, and sodium bicarbonate. Medications that might worsen the condition should be stopped and a low potassium diet should be started. Measures to remove potassium from the body include diuretics such as furosemide, potassium-binders such as polystyrene sulfonate and sodium zirconium cyclosilicate, and hemodialysis. Hemodialysis is the most effective method. Hyperkalemia is rare among those who are otherwise healthy. Among those who are hospitalized, rates are between 1% and 2.5%. It is associated with an increased mortality, whether due to hyperkalaemia itself or as a marker of severe illness, especially in those without chronic kidney disease. The word hyperkalemia comes from hyper- 'high' + kalium 'potassium' + -emia 'blood condition'.

Potassium

Renal filtration, reabsorption, and excretion Renal handling of potassium is closely connected to sodium handling. Potassium is the major cation (positive ion) inside animal cells [150mmol/L, (4.8g)], while sodium is the major cation of extracellular fluid [150mmol/L, (3.345g)]. In the kidneys, about 180liters of plasma is filtered through the glomeruli and into the renal tubules per day. This filtering involves about 600g of sodium and 33g of potassium. Since only 1–10g of sodium and 1–4g of potassium are likely to be replaced by diet, renal filtering must efficiently reabsorb the remainder from the plasma.

Severe Persistent Hyperkalemia with Electrocardiogram Changes in a Patient with Hyperaldosteronism.

A 62-year-old female presented to the emergency department (ED) with fatigue and generalized body weakness for the last three days. Upon arrival, initial ECG showed wide complex tachycardia with sine waves and a heart rate (HR) ranging between 100-170 bpm. She was otherwise vitally stable. The patient had a past medical history of hyperaldosteronism, type 2 diabetes mellitus (DM), chronic kidney disease (CKD) with microalbuminuria, and hypertension. She also had a history of cerebrovascular accident (CVA) and residual left-sided weakness more pronounced in the upper limb. Initial venous blood gas (VBG) analysis showed a potassium level of more than 10 mmol/L, chloride 114 mmol/L, bicarbonate 9 mmol/L, sodium 135 mmol/L, and pH of 7.1. Treatment for hyperkalemia was started immediately with calcium gluconate 1 gm that effectively narrowed her QRS complex and normalized her ECG. Salbutamol nebulization, glucose/insulin infusion, and calcium polystyrene syrup were given. Later, she was started on 100 mg sodium bicarbonate infusion, and Foley's catheter was inserted to follow urine output (UOP) strictly. However, she did not show a decrease in serum potassium levels. Then the patient underwent hemodialysis for two hours. Her first potassium reading after hemodialysis was 5.2 mmol/L. The purpose of this case report is to emphasize the importance of hemodialysis in patients with persistent severe life-threatening hyperkalemia.

First_Aid_Step2

FIGURE 2.16-1. Hyperkalemia on ECG. Hypokalemia is usually due to renal or GI losses Hypokalemia sensitizes the heart to digitalis toxicity because K+ and digitalis compete for the same sites on the Na+/K+ pump, so if a patient is on digitalis, potassium levels must be carefully monitored. Electrocardiographic manifestations include peaked T waves, PR prolongation, and a widened QRS complex. (Reproduced, with permission, from Cogan MG. Fluid and Electrolytes, 1st ed. Stamford, CT: Appleton & Lange, 1991: 170.) Values of > 6.5 mEq/L or ECG changes (especially PR prolongation or wide QRS) require emergent treatment. The mnemonic C BIG K summarizes the treatment of hyperkalemia. First give calcium gluconate for cardiac cell membrane stabilization. Give bicarbonate and/or insulin and glucose to temporarily shift potassium into cells. β-agonists (e.g., albuterol) promote cellular reuptake of potassium. Eliminate potassium from diet and IV ﬂ uids.

Hypokalemia

In the heart, hypokalemia causes arrhythmias because of less-than-complete recovery from sodium-channel inactivation, making the triggering of an action potential less likely. In addition, the reduced extracellular potassium (paradoxically) inhibits the activity of the IKr potassium current and delays ventricular repolarization. This delayed repolarization may promote reentrant arrhythmias. Diagnosis Blood Normal potassium levels are between 3.5 and 5.0 mmol/L with levels below 3.5 mmol/L (less than 3.5 mEq/L) defined as hypokalemia. Electrocardiogram Hypokalemia leads to characteristic ECG changes (PR prolongation, ST-segment and T-wave depression, U-wave formation).

Acute and chronic cardiovascular effects of hyperkalemia: new insights into prevention and clinical management.

The plasma pool of potassium is a partial reflection of the overall body, transient cellular shifts, and potassium elimination regulated by the kidneys. Potassium concentrations elevating above the upper limit of normal (> 5.0 mEq/L) have become more common in cardiovascular practice due to the growing population of patients with chronic kidney disease and the broad applications of drugs that modulate potassium excretion by either reducing production of angiotensin II (angiotensin-converting enzyme inhibitors, direct renin inhibitors, beta-adrenergic receptor antagonists), blocking angiotensin II receptors (angiotensin receptor blockers), or antagonizing the action of aldosterone on mineralocorticoid receptors (mineralocorticoid receptor antagonists). In addition, acute kidney injury, critical illness, crush injuries, and massive red blood cell transfusions can result in hyperkalemia. Progressively more severe elevations in potassium are responsible for abnormalities in cardiac depolarization and repolarization and contractility. Untreated severe hyperkalemia results in sudden cardiac death. Traditional management steps have included reducing dietary potassium and discontinuing potassium supplements; withdrawal of exacerbating drugs; acute treatment with intravenous calcium gluconate, insulin, and glucose; nebulized albuterol; correction of acidosis with sodium bicarbonate for short-term shifts out of the plasma pool; and, finally, gastrointestinal ion exchange with oral sodium polystyrene sulfonate in sorbitol, which is mainly used in the hospital and is poorly tolerated due to gastrointestinal adverse effects. This review explores hyperkalemia as a complication in cardiovascular patients and highlights new acute, chronic, and preventative oral therapies (patiromer calcium, cross-linked polyelectrolyte, ZS-9) that could potentially create a greater margin of safety for vulnerable patients with combined heart and kidney disease.

Hypokalemia

Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abnormal heart rhythm, which is often too slow and can cause cardiac arrest. Causes of hypokalemia include vomiting, diarrhea, medications like furosemide and steroids, dialysis, diabetes insipidus, hyperaldosteronism, hypomagnesemia, and not enough intake in the diet. Normal potassium levels are between 3.5 and 5.0 mmol/L (3.5 and 5.0 mEq/L) with levels below 3.5 mmol/L defined as hypokalemia. It is classified as severe when levels are less than 2.5 mmol/L. Low levels may also be suspected based on an electrocardiogram (ECG). Hyperkalemia is a high level of potassium in the blood serum.

Hyperkalemia

Exercise can cause a release of potassium into bloodstream by increasing the number of potassium channels in the cell membrane. The degree of potassium elevation varies with the degree of exercise, which range from 0.3 meq/L in light exercise to 2 meq/L in heavy exercise, with or without accompanying ECG changes or lactic acidosis. However, peak potassium levels can be reduced by prior physical conditioning and potassium levels are usually reversed several minutes after exercise. High levels of adrenaline and noradrenaline have a protective effect on the cardiac electrophysiology because they bind to beta 2 adrenergic receptors, which, when activated, extracellularly decrease potassium concentration.

Potassium -- Mechanism of Action

As a major intracellular cation, potassium acts to preserve acid-base balance and maintain isotonicity and electrodynamic cellular function. It activates many enzymatic reactions within our body. It plays an essential role in the transmission of nerve impulses, contraction of cardiac muscles, skeletal and smooth muscles, tissue synthesis, gastric secretion, and renal function. Potassium reduces mean systolic and diastolic blood pressure. [1] Normal serum potassium values are between 3.5 and 5.0 millimoles/L (mmol/L). Levels outside this range correlate with increased rates of death from several causes. [7] [8]

Potassium

Control mechanisms Potassium content in the plasma is tightly controlled by four basic mechanisms, which have various names and classifications. The four are 1) a reactive negative-feedback system, 2) a reactive feed-forward system, 3) a predictive or circadian system, and 4) an internal or cell membrane transport system. Collectively, the first three are sometimes termed the "external potassium homeostasis system"; and the first two, the "reactive potassium homeostasis system". The reactive negative-feedback system refers to the system that induces renal secretion of potassium in response to a rise in the plasma potassium (potassium ingestion, shift out of cells, or intravenous infusion.)

Diagnosis and clinical approach in Gitelman's syndrome.

Hypokalemia, defined as a plasma potassium concentration <3.5 mmol/l, is the most common electrolyte abnormality encountered in our clinical practice. Unfortunately, in many cases, the etiologies were unclear and resulted in a wrong treatment. Indeed, the true etiology could be such a 'rare' one and could be found by doing a comprehensive work up. One of this is Gitelman's syndrome, a rare genetic disorder characterized by hypokalemic alkalosis, hypomagnesemia, hypocalciuria, and secondary aldosteronism without hypertension. Since this disorder is found in 1% Caucasian populations, this is one of the most frequently inherited renal tubular disorders. A 27 year old man came to emergency room with weakness and generalised muscle cramps. He was investigated three months before for a similar electrolyte disturbance which was found to be inconclusive. The routine laboratory data in emergency room revealed a potassium concentration of 2.3 mmol/l. He had never used diuretics or hormonal therapy nor had history of vomiting or diarrhea. He had normal blood pressure and the blood gas analysis revealed metabolic alkalosis. On his ECG (electrocardiography), we found the prominent U wave. Despite his low concentration of serum potassium and cloride, the concentration of these electrolytes in urine were extremely high. We also found hipomagnesemia. The calcium concentration in serum was normal with slightly hypocalciuria. Even with aggressive oral and intravenous potassium suplementation, the patient remained hypokalemic. In cases when the etiology of hypokalemia is unclear, we should perform some investigations to confirm the diagnosis and give the proper treatment. In Gitelman's syndrome, where the defect in the distal tubule cannot be corrected, the treatment must be a life-long. Most patients require oral potassium and magnesium supplementation, since drug therapy is usually incompletely effective.

Rhabdomyolysis

Electrolytes In the initial stages, electrolyte levels are often abnormal and require correction. High potassium levels can be life-threatening, and respond to increased urine production and renal replacement therapy (see below). Temporary measures include the administration of calcium to protect against cardiac complications, insulin or salbutamol to redistribute potassium into cells, and infusions of bicarbonate solution. Calcium levels initially tend to be low, but as the situation improves calcium is released from where it has precipitated with phosphate, and vitamin D production resumes, leading to hypercalcemia (abnormally high calcium levels). This "overshoot" occurs in 20–30% of those people who have developed kidney failure. Acute kidney impairment

Case report: MRI findings of acute uremic encephalopathy in a 1-year-old boy.

We present a 1-year-old boy who presented to the emergency department with a 7-day history of diarrhoea and vomiting. The initial renal function profile demonstrated a urea of 55 mmol l<sup-1</sup (normal range between 5 and 20 mmol l<sup-1</sup), creatinine 695 micromol/L (normal range between 62-106 micromol/L) and potassium 9.1 mmol l<sup-1</sup (normal range between 3.5-5.0 mmol l<sup-1</sup), with a profound metabolic acidosis. Upon examination, there were no significant findings, specifically no neurological abnormality. He was prescribed back-to-back Salbutamol nebulisers, to increase the shift of extracellular potassium into the intracellular space, followed by i.v. calcium gluconate, with some improvement in potassium levels. A further 5 mmol of sodium bicarbonate was given, as well as a stat dose of 1 mg/kg furosemide, and per rectal calcium resonium. He was then commenced on an infusion with 10% dextrose with insulin. He was subsequently found to be in urinary retention and a catheter was inserted, which drained 1700 ml. A subsequent renal function profile, 24 hours after admission, demonstrated improvement with urea 39 mmol l<sup-1</sup, creatinine 300 micromol/L and potassium 3.0 mEq/L.