The correct answer is: 2. Focal segmental glomerulonephritis. We are in front of a patient with renal insufficiency whose manifestation is a proteinuria. That places us in the picture of nonproliferative GN (membranous, focal and segmental and minimal changes, discarding the other two). If we also consider that the patient was obese, slightly hypertensive, the most probable is that it is a focal segmental glomerulonephritis.

The [HIDDEN]. We are in front of a patient with renal insufficiency whose manifestation is a proteinuria. That places us in the picture of nonproliferative GN (membranous, focal and segmental and minimal changes, discarding the other two). If we also consider that the patient was obese, slightly hypertensive, the most probable is that it is a focal segmental glomerulonephritis.

A 58-year-old woman, weight 130 kg, height 155 cm, body mass index > 30 with mild hypertension, blood glucose 108 mg/dL and absence of edema in the lower limbs. Blood analysis showed Cr 2.0 mg/dL, Urea 86 mg/dL, Alb 3.8 g/1, Na 142 mEq/L, K 4 mEq/L. In urinalysis: sediment without alterations and in 24 h urine proteinuria of 6.3 g/24 h. Which of the following entities is more likely to be present?

Renal biopsy findings and clinical indicators of patients with hematuria without overt proteinuria.

Whether to perform a renal biopsy for isolated hematuria remains a matter of controversy. We performed renal biopsy in hematuria without overt proteinuria patients and reported the proportion of glomerulonephritis, pathological activities, and statistical analysis of indicators associated with glomerulonephritis. Among 203 patients who underwent renal biopsy in Okubo Hospital, Japan, between January 2008 and October 2013, we identified 56 patients who fulfilled the criteria: (1) urine dipstick examination shows equal to or greater than ± blood on three or more visits, (2) proteinuria <0.3 g/day (g/g Cr), (3) eGFR ≧60 ml/min/1.73 m(2), and (4) no current medication for renal disease. We investigated biopsy findings and compared the clinical indicators in the IgA nephropathy (IgAN) and non-IgAN group. The pathological diagnosis was IgAN in 35 cases (62 %), thin basement membrane disease (TBMD) in 7 (13 %), minor glomerular abnormality (MGA) in 6 (11 %), glomerular basement membrane (GBM) abnormality in 5 (9 %), and others in 3 (5 %). The histological grade of IgAN was I in 90 % and II in 10; 31 % of patients had some crescentic lesions. Comparisons between the IgAN and non-IgAN group revealed significant differences in age of onset (26 ± 13 vs. 34 ± 17 years, p = 0.04), serum IgA (340 ± 114 vs. 220 ± 101 mg/dl, p < 0.01), proteinuria (0.08 [0-0.25] vs. 0 [0-0.23] g/day [g/gCr], p < 0.01), and the presence of poikilocytes (40 vs. 10 %, p = 0.02). The proportion of IgAN in hematuria without overt proteinuria was high and the pathological activities were variable. Patients with hematuria without overt proteinuria should continue their medical follow-up and the best timing of biopsy may be controversial for these patients who have multiple risk factors of IgAN.

Crescentic IgA nephropathy.

We report five cases of crescentic IgA nephropathy. All are males, 16-60 years of age. One case each came to medical attention with uremia, nephrotic syndrome, and gross hematuria; two cases presented with microhematuria and proteinuria on routine urinalysis. All had hypertension, azotemia (serum creatinine 1.6-9.4 mg/dl), proteinuria (greater than 6 g/24 hr in four cases), hypoalbuminemia (less than 3 g/dl), and hematuria (gross in two cases). All progressed to end-stage renal failure renal failure ending in dialysis (three cases) or death from unrelated causes (two cases). Prednisone, 60 mg/day for 1 month in two patients (with two 1-g doses of iv methylprednisolone in 1 case) did not improve the serum creatinine level, but one patient subsequently experienced a less rapid fall in renal function. A crescentic glomerulonephritis was present in all biopsies (crescents in 31-80% of glomeruli; mean, 50%). The size and stage of the crescents were variable. Numerous glomeruli had focal or diffuse sclerosis. In all cases, there was a 3 or 4+ deposition of IgA. Low-intensity staining for IgG and IgM was noted in four and three patients, respectively. On electron microscopy, dense granular mesangial deposits were noted in all cases and in four patients capillary subepithelial deposits were also observed. This form of IgA nephropathy is not common, but some studies indicate that it may occur in about 5% of patients with IgA nephropathy.

IgA nephropathy. Evaluation of prognostic factors in patients with moderate disease.

Previous studies of IgA nephropathy have demonstrated a number of prognostically significant clinical and pathological factors in groups of patients with the full histological spectrum of the disease. Whether these factors can be applied to a group of IgA nephropathy patients with disease of moderate degree is unknown. Forty patients (9 females, 31 males) with grade III IgA nephropathy (no more than 10% obsolete glomeruli and little or no interstitial fibrosis) were evaluated with respect to age, sex, degree of proteinuria, history of recurrent gross hematuria, hypertension, extent and type of segmental glomerulosclerosis, demonstration of IgG and/or IgM in deposits, presence of peripheral capillary deposits, whether or not there were crescents, and extent of vascular sclerosis. The mean age was 29.6 +/- (SD) 13.1 years. Sixteen patients presented with recurrent gross hematuria, and 24 had microscopic hematuria and proteinuria as the initial manifestation. Hypertension was seen in 5 patients. The mean serum creatinine concentration was 1.09 +/- 0.47 mg/dl (96.4 +/- 41.5 mumol/l), and the mean 24-hour urinary protein was 1.5 +/- 1.3 g. Nine patients had proteinuria greater than or equal to 2.0 g/24 h. Thirty-two patients demonstrated segmental glomerulosclerosis in their biopsies, 13 of which had more than 10% of the glomeruli involved. Seven patients developed established renal failure (Cr greater than or equal to 2.0 mg/dl; 176.8 mumol/l). The 60-and 100-month renal survival rates were 96 and 52%. Life table analysis disclosed that only the degree of proteinuria (greater than or equal to 2.0 g/24 h; p less than 0.05) and the extent of segmental glomerulosclerosis (p less than 0.025) were of prognostic significance.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of anti-GBM nephritis (crescentic glomerulonephritis) associated with membranous nephropathy].

We report a case of endstage renal disease due to simultaneous occurrence of membranous nephropathy and crescentic glomerulonephritis associated with anti-GBM antibodies. The patient was a 60-year-old male and was hospitalized for prolonged anorexia and general malaise. On admission, his body temperature was 38.5 degrees C. Urinalysis revealed 3+ proteinuria and the sediment contained abundant erythrocytes. The urea nitrogen was 142.4 mg/dl, the creatinine 19.5 mg/dl, the potassium 6.47 mEq/dl and CRP 10.1 mg/dl. Anti-GBM antibodies were 1000EU/ml. Immediately after initiating hemodialysis, pulse steroid therapy, plasma exchange and continuous heparinization were performed. However, renal function had been impaired and maintenance hemodialysis was required. Histological examination of the renal specimen revealed marked epithelial crescent formation, whereas thickening of basement membrane and mesangial proliferation were not observed. By immunofluorescent staining, both bright linear and fine granular fixation of IgG and fine granular fixations of C3 along the glomerular capillary walls were observed. Electron microscopy showed subepithelial electron lucent deposits and thickening of the glomerular basement membrane, diagnostic of the advanced membranous nephropathy (stage IV).

Glomerulonephritis

Proliferative Proliferative glomerulonephritis is characterised by an increased number of cells in the glomerulus. These forms usually present with a triad of blood in the urine, decreased urine production, and hypertension, the nephritic syndrome. These forms usually progress to end-stage kidney failure (ESKF) over weeks to years (depending on type). IgA nephropathy IgA nephropathy, also known as Berger's disease, is the most common type of glomerulonephritis, and generally presents with isolated visible or occult hematuria, occasionally combined with low grade proteinuria, and rarely causes a nephritic syndrome characterised by protein in the urine, and visible blood in the urine. IgA nephropathy is classically described as a self-resolving form in young adults several days after a respiratory infection. It is characterised by deposits of IgA in the space between glomerular capillaries.

Membranous glomerulonephritis

Membranous glomerulonephritis (MGN) is a slowly progressive disease of the kidney affecting mostly people between ages of 30 and 50 years, usually white people (ie, those of European, Middle Eastern, or North African ancestry.). It is the second most common cause of nephrotic syndrome in adults, with focal segmental glomerulosclerosis (FSGS) recently becoming the most common. Signs and symptoms Most people will present as nephrotic syndrome, with the triad of albuminuria, edema and low serum albumin (with or without kidney failure). High blood pressure and high cholesterol are often also present. Others may not have symptoms and may be picked up on screening, with urinalysis finding high amounts of protein loss in the urine. A definitive diagnosis of membranous nephropathy requires a kidney biopsy, though given the very high specificity of anti-PLA2R antibody positivity this can sometimes be avoided in patients with nephrotic syndrome and preserved kidney function Causes

IgA nephropathy

A smaller proportion (20–30%), usually the older population, have microscopic hematuria and proteinuria (less than 2 gram/day). These patients may be asymptomatic and only picked up due to urinalysis. Hence, the disease is more commonly diagnosed in situations where screening of urine is compulsory (e.g., schoolchildren in Japan). Very rarely (5% each), the presenting history is: Nephritic syndrome Acute kidney failure (either as a complication of the frank hematuria, when it usually recovers or due to rapidly progressive glomerulonephritis which often leads to chronic kidney failure) Chronic kidney failure (no previous symptoms, presents with anemia, hypertension and other symptoms of kidney failure, in people who probably had longstanding undetected microscopic hematuria and/or proteinuria)

InternalMed_Harrison

PROTEINURIA ON URINE DIPSTICK Quantify by 24-h urinary excretion of protein and albumin or first morning spot albumin-to-creatinine ratio RBCs or RBC casts on urinalysis In addition to disorders listed under microalbuminuria consider Myeloma-associated kidney disease (check UPEP) Intermittent proteinuria Postural proteinuria Congestive heart failure Fever Exercise Go to Fig. 61-2 Macroalbuminuria 300-3500 mg/d or 300-3500 mg/g Microalbuminuria 30-300 mg/d or 30-300 mg/g Nephrotic range > 3500 mg/d or > 3500 mg/g + Consider Early diabetes Essential hypertension Early stages of glomerulonephritis (especially with RBCs, RBC casts)Consider Early diabetes Essential hypertension Early stages of glomerulonephritis (especially with RBCs, RBC casts) Nephrotic syndrome Diabetes Amyloidosis Minimal change disease FSGS Membranous glomerulopathy IgA nephropathy

Nephrotic syndrome

The main signs of nephrotic syndrome are: A proteinuria of greater than 3.5 g /24 h /1.73 m2 (between 3 and 3.5 g/24 h /1.73 m2 is considered to be proteinuria in the nephrotic range) or greater than 40 mg/h/m2 in children. The ratio between urinary concentrations of albumin and creatinine can be used in the absence of a 24-hour urine test for total protein. This coefficient will be greater than 200–400 mg/mmol in nephrotic syndrome. This pronounced loss of proteins is due to an increase in glomerular permeability that allows proteins to pass into the urine instead of being retained in the blood. Under normal conditions a 24-hour urine sample should not exceed 80 milligrams or 10 milligrams per decilitre. A hypoalbuminemia of less than 2.5 g/dL, that exceeds the liver clearance level, that is, protein synthesis in the liver is insufficient to increase the low blood protein levels.

Ranson criteria

Acute pancreatitis not secondary to gallstones At admission: Blood glucose > 11.11 mmol/L (> 200 mg/dL) Age > 55 years Serum LDH > 350 IU/L Serum AST > 250 IU/L WBC count > 16000 cells/mm3 Within 48 hours: Serum calcium < 2.0 mmol/L (< 8.0 mg/dL) Hematocrit decreased by > 10% Oxygen (hypoxemia with PaO2 < 60 mmHg) BUN increased by 1.8 or more mmol/L (5 or more mg/dL) after IV fluid hydration Base deficit (negative base excess) > 4 mEq/L Sequestration of fluids > 6 L Acute pancreatitis secondary to gallstones At admission: Glucose > 220 mg/dl Age > 70 years LDH > 400 IU/L AST > 250 IU/ 100 ml WBC count > 18000 cells/mm3 Within 48 hours: Serum calcium < 8 mg/dL Hematocrit decreased by > 10% Base deficit > 4 mEq/L BUN increased by > 2 mg/dL Sequestered fluid > 6L

[The survival of patients with mesangial immunoglobulin A glomerulonephritis].

68 patients with immunoglobulin A glomerulonephritis (IgA-GN) were studied. 67.4% of them were men. The most frequent clinical manifestation is the microscopical hematuria--in 39.7% of the patients. A single episode of macroscopic hematuria was found in 32.3% of the patients and recurrent macroscopic hematuria--in 25% of the patients. Proteinuria was found in all patients but nephrotic syndrome--only in one patient. At the time of the biopsy 35.5% of the patients were with hypertension, 13.2%--with initial chronic renal failure. The survival of the patients with IgA--GN, assessed according to the registration life tables, was 93% at the 5-th year, 88% at the 10-th year and 70.6% at the 20-th year. It was statistically higher in the patients without hypertension. Among the patients with proteinuria below 1.0/24 h no one reached terminal chronic renal failure. The male sex was a factor for a statistically shorter survival only at the 20-th year. The survival of the patients with insignificant histological changes was 100% for the period of the study, whereas it was significantly lower for the other histological variants. According to the data of the study, the presence of arterial hypertension, proteinuria above 1.0 g/24 h, a more severe histological variant (focal-segment, diffuse proliferative and particularly sclerotic), and to a certain degree the male sex play an unfavorable role in the survival and determine a poorer prognosis for the patients with IgA-GN.

Nabumetone-associated interstitial nephritis.

An 84-year-old woman was admitted to the hospital for progressive edema and decreased urine output. She had been taking nabumetone for 6 months, but had discontinued the agent 2 weeks before admission due to progressive edema. On admission she had 2-3+ pitting edema. Her serum electrolytes were sodium 122 mEq/L, potassium 5.9 mEq/L, chloride 93 mEq/L, and carbon dioxide 19 mEq/L. A urinalysis was significant for protein 3061 mg/dl, ketones 15 mg/dl, blood 2+, leukocytes 26-50/high-power field, and a protein:creatinine ratio 24.9. The serum creatinine and blood urea nitrogen concentrations were 2.7 mg/dl and 70 mg/dl, respectively. Throughout hospitalization the patient underwent aggressive diuresis. She developed congestive heart failure, and hemodialysis was initiated. A renal biopsy specimen on hospital day 9 showed tubular damage with minimal glomerular changes consistent with a diagnosis of nonsteroidal agent-induced nephropathy. On day 13, a 24-hour urine collection had a protein excretion of 3151 mg. Although the patient recovered from her renal failure (creatinine clearance 43 ml/min), the nephrotic syndrome persisted (13 g protein/day). The patient developed infectious complications and died on hospital day 32.

[Clinico-morphological features and the course of glomerulonephritis in hemorrhagic vasculitis].

Peculiarities of a clinical course and prognosis of glomerulonephritis in Schönlein-Henoch disease (SH-nephritis) were studied in 42 adult patients. The 5- and 10-year survival rates were 87% and 72%, respectively. Of unfavorable prognostic value were proteinuria over 1 g/l, nephrotic syndrome, particularly combined with hypertension, marked stable microhematuria, and the detection of diffuse fibroplastic, extracapillary, and mesangiocapillary nephritis on biopsy. SH-nephritis was characterized by a more severe course in male patients, in persons aged over 30, and in the involvement of the kidneys one year and more after the appearance of the first clinical signs of skin vasculitis. The level of blood serum IgA and the gravity of skin vasculitis had no prognostic importance.

Efonidipine reduces proteinuria and plasma aldosterone in patients with chronic glomerulonephritis.

Efonidipine, a dihydropirydine calcium channel blocker, has been shown to dilate the efferent glomerular arterioles as effectively as the afferent arterioles. The present study compared the chronic effects of efonidipine and amlodipine on proteinuria in patients with chronic glomerulonephritis. The study subjects were 21 chronic glomerulonephritis patients presenting with spot proteinuria greater than 30 mg/dL and serum creatinine concentrations of <or=1.3 mg/dL in men or <or=1.1 mg/dL in women. All patients were receiving antihypertensive medication or had a blood pressure >or=130/85 mmHg. Efonidipine 20-60 mg twice daily and amlodipine 2.5-7.5 mg once daily were given for 4 months each in a random crossover manner. In both periods, calcium channel blockers were titrated when the BP exceeded 130/85 mmHg. Blood sampling and urinalysis were performed at the end of each treatment period. The average blood pressure was comparable between the efonidipine and the amlodipine periods (133+/-10/86+/-5 vs. 132+/-8/86+/-5 mmHg). Urinary protein excretion was significantly less in the efonidipine period than in the amlodipine period (1.7+/-1.5 vs. 2.0+/-1.6 g/g creatinine, p=0.04). Serum albumin was significantly higher in the efonidipine period than the amlodipine period (4.0+/-0.5 vs. 3.8+/-0.5 mEq/L, p=0.03). Glomerular filtration rate was not significantly different between the two periods. Plasma aldosterone was lower in the efonidipine period than in the amlodipine period (52+/-46 vs. 72+/-48 pg/mL, p=0.009). It may be concluded that efonidipine results in a greater reduction of plasma aldosterone and proteinuria than amlodipine, and that these effects occur by a mechanism independent of blood pressure reduction. A further large-scale clinical trial will be needed in order to apply the findings of this study to the treatment of patients with renal disease.

The Pisa experience of renal biopsies, 1977-2005.

Although several registries collecting data of patients with kidney diseases exist, only a few specifically collect data relating to renal biopsy. Kidney biopsy has been performed routinely in Pisa since 1977; the aim of this study was to report the relative frequency of nephropathies according to gender, age at time of biopsy, clinical presentation and renal function, based on histological diagnoses during the years 1977 through 2005. During this time, 3,810 kidney biopsies were performed, of which 89.3% were from native (n=3,446) and 10.7% from transplant kidneys. Throughout this period, 5% of renal biopsies were not diagnostic, so in this paper we report data regarding 3,269 native kidney nephropathies. During the years 1977 through 2005, data for renal biopsies were collected on specific registers filled out by clinicians. Information collected in the database included a variety of indicators, such as clinical anamnesis, creatinine clearance, daily proteinuria, hemoglobin levels, blood pressure, height and weight, clinical presentation, and current medications. Clinical presentation was defined as urinary abnormalities (UA), nephrotic syndrome (NS) and acute nephritic syndrome (ANS). Renal diseases were divided into 4 major categories: primary glomerulonephritis (GN), secondary GN, tubulointerstitial nephropathies (TIN) and vascular nephropathies (VN). From 1977 up to 1987, a mean of 95 +/- 18 renal biopsies/year were performed; this number significantly increased to 185 +/- 22 renal biopsies/year (range 138-200) (p<0.001) in the following period (1988-2005). Renal biopsy was more frequently performed in males (59%) compared with females (41%). Of all diseases of the native kidney, primary GN was the most frequent (66%), followed by secondary GN (25.6%), TIN (4.2%) and VN (4.2%). The type of primary GN with the highest frequency was mesangial GN (both IgA and non-IgA) (45.7%), followed by membranous GN (23%), focal segmental glomerulosclerosis (19.8%), minimal change disease (5.3%), crescentic GN (4.2%) and postinfectious GN (2%). In terms of age, renal biopsy was more frequently performed in patients aged 20 to 60 years, and nearly 60% of patients presented a glomerular filtration rate (GFR) >60 ml/min at the time of biopsy. The main clinical reason for performing renal biopsy was UA, in all the types of nephropathies. We confirm data that renal diseases are more frequent in men, with the exception of secondary GN. The mean age at diagnosis was 42 years resulting from the tendency not to perform renal biopsies in children and in elderly patients. Renal biopsy was mainly performed in patients with GFR >60 ml/min and asymptomatic urinary abnormalities suggesting concern on the part of clinicians regarding glomerular diseases. The tendency to perform renal biopsies has been significantly increasing throughout our follow-up period.

Idiopathic membranous glomerulonephritis: a clinicopathologic and quantitative morphometric study.

We evaluated clinical and morphological findings in 254 patients (138 men and 116 women), with idiopathic membranous glomerulonephritis (IMGN). The mean age was 44 years. At time of biopsy proteinuria was found in 98%, nephrotic syndrome (NS) in 45.2%, hypertension in 10%, elevated serum creatinine concentration of greater than or equal to 1.4 g/dl in 24%, and markedly decreased Ccr (less than or equal to 40 ml/min) in 12.5% of the patients. Of 254 patients, 51 (20%) were classified as Stage I, 131 (52%) as Stage II, 52 (20.5%) as Stage III, 9 (3.5%) as Stage IV and 11 (4.3%) as Stage V, which was a relapsing form. Both intraglomerular, peripheral electron dense deposit-size and mean thickness of the glomerular basement membrane (GBMt) were analyzed by ultrastructural morphometric methods. In patients with NS, both the mean deposit-size and the mean GBMt were largest when compared to all others (p less than 0.01). The largest subepithelial deposits (SED), in mean, were observed in Stages II and V, while the largest incorporated deposits (ICD) were measured in Stages II and IV. The mean GBMt was largest in Stage III. Furthermore, there were strong correlations between the degree of proteinuria and the deposit-size (r = 0.603, p less than 0.001), and GBMt (r = 0.456, p less than 0.001). The GBMt showed a correlation with serum creatinine concentration (r = 0.476, p less than 0.001) and Ccr (r = 0.471, p less than 0.001). We concluded that the size of the electron dense deposits and GBM thickness play an important role in the clinical manifestation of IMGN.

Hypertensive disease of pregnancy

Preeclampsia superimposed on chronic hypertension occurs when a pregnant woman with chronic hypertension develops signs of pre-eclampsia, typically defined as new onset of proteinuria ≥30 mg/dL (1+ in the dipstick) in at least 2 random urine specimens that were collected ≥4 h apart (but within a 7-day interval) or 0.3 g in a 24-h period. Like ordinary pre-eclampsia, superimposed pre-eclampsia can also occur with severe features, which are defined as: systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥110 mmHg despite escalation of antihypertensive therapy; thrombocytopenia (platelet count <100,000/microL); impaired liver function; new-onset or worsening renal insufficiency; pulmonary edema; or persistent cerebral or visual disturbances. As a result, superimposed pre-eclampsia can be diagnosed without proteinuria when a sudden increase in previously well-controlled blood pressure is accompanied by severe features of pre-eclampsia.

Maximal glomerular diameter as a 10-year prognostic indicator for IgA nephropathy.

Although there have been many reports on clinicopathological studies of immunoglobulin A nephropathy (IgAN), reliable outcome predictors are still lacking. We therefore assessed maximal glomerular diameter (Max GD), an indicator of glomerular size, as a predictor of the long-term evolution of renal histopathology. Forty-three adult patients, diagnosed with IgAN, who had estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73 m(2), were enrolled in this study. Prognostic variables for renal survival were examined by using the multivariate Cox proportional hazards method. The optimal cut-off value of Max GD was 242.3 μm (AUC = 0.78, sensitivity = 62.5%, specificity = 81.5%) by using receiver operating characteristics analysis. In order to assess the characteristics of glomerular hypertrophy, we divided the cases into two groups according to the Max GD value (Group A, ≥242 μm; Group B, <242 μm). Renal survival was also assessed by Kaplan-Meier curves with the log-rank test. The Max GD was significantly correlated with age, body mass index and serum triglyceride levels at the time of renal biopsy. During the 10-year follow-up period, the Max GD was significantly correlated with eGFR decline per year, and proteinuria, but not with hematuria. A multiple regression analysis by the Cox method adjusted for age, sex and eGFR showed that the Max GD values were significantly associated with a 1.5-fold increase in serum creatinine (Cr) values (hazard ratio = 1.04, P = 0.03). Renal function in 66.7% of the patients whose Max GD was ≥242 μm had at least a 1.5-fold increase in their serum Cr value at the 10-year follow-up examination (log-rank, P = 0.003). The results of this study suggest that Max GD is a simple quantitative prognostic indicator of the disease progression in IgAN patients.

Acquired glomerular lesions in patients with Down syndrome.

The long-term survival of persons with Down syndrome has dramatically increased over the past 50 years. There are no studies addressing the spectrum of glomerular lesions in these patients. We reviewed the clinical-pathologic characteristics of 17 patients with Down syndrome who underwent renal biopsy. The cohort consisted of 12 whites and 5 African Americans with mean age of 29 years (range, 6-45 years). History of hypothyroidism was present in 8 patients. Renal presentations included renal insufficiency (15 patients, mean serum creatinine 3.4 mg/dL), proteinuria (all patients, including 3 with nephrotic syndrome, mean 24-hour urine protein 4.2 g), and hematuria (14 patients, including 4 with gross hematuria). The glomerular diseases found on biopsy were IgA nephropathy (n = 5 patients), focal segmental glomerulosclerosis (n = 4), membranoproliferative glomerulonephritis (n = 2), acute postinfectious glomerulonephritis (n = 2), pauci-immune crescentic glomerulonephritis (n = 2), membranous glomerulonephritis (n = 1), and lupus nephritis (n = 1). Follow-up (mean, 47 months; range, 2-141 months) was available on 16 patients (94%). Two patients (1 with membranous glomerulonephritis and 1 with acute postinfectious glomerulonephritis) had complete remission; 8 patients (4 with IgA nephropathy, 2 with focal segmental glomerulosclerosis, 1 with lupus nephritis, and 1 with acute postinfectious glomerulonephritis) had chronic kidney disease; and 6 patients (2 with pauci-immune crescentic glomerulonephritis, 2 with membranoproliferative glomerulonephritis, 1 with IgA nephropathy, and 1 with focal segmental glomerulosclerosis) progressed to end-stage renal disease, 4 of whom died. In summary, a wide spectrum of glomerular diseases can be seen in patients with Down syndrome, with IgA nephropathy and focal segmental glomerulosclerosis being the most common. Renal biopsy is necessary to determine the type of glomerular lesion and appropriate treatment.

[Renal histological lesions in patients with type II diabetes mellitus].

Diabetic glomerulosclerosis is the most frequent cause of renal disease in patients with type II diabetes mellitus (DM), sometimes accompanied by vascular lesions. However, other glomerular pathologies are important in these patients. The aim of this study was to evaluate the prevalence of non-diabetic nephropathy (NDN) in selected patients with type II DM, and to identify clinical markers that may predict its presence in this population. We reviewed 20 renal biopsies performed on twenty patients with type II DM. Nine of them showed diabetic nephropathy (DN) (45%), whereas eleven showed NDN (55%): 1 IgA nephropathy, 3 vasculitis and 7 membranous nephropathy. We found no differences between the two groups with regard to sex, duration of DM, insulin therapy, glycosylated haemoglobin, proteinuria, presence of nephrotic syndrome, hypertension, serum IgA level or renal size. The NDN group had haematuria in 63.6%, whereas the patients with NDN had it in 44.4% (NS). Body mass index was higher in NDN patients (30 +/- 6.7 vs 22 +/- 2.9; p < 0.01), The same was true for creatinine clearance (82.2 +/- 51.4 ml/m vs 40.4 +/- 19.6 ml/m; p < 0.05). The age at the moment of diagnosis was higher in ND patients (67 +/- 11.2 vs 54.3 +/- 4.6; p < 0.05). The 3 patients who had diabetic retinopathy were found to have DN on renal biopsy (diagnostic specificity = 100%), although 66.7% of the patients with diabetic glomerulopathy had no retinopathy. We conclude that patients with type II DM with renal findings suggesting non-diabetic renal disease frequently it have NDN, and a renal biopsy must be performed. The presence of retinopathy has a predictive value of 100% in predicting DN, therefore its existence may make this diagnostic procedure unneccesary.

Glucose tolerance test

For gestational diabetes, the American College of Obstetricians and Gynecologists (ACOG) recommends a two-step procedure, wherein the first step is a 50 g glucose dose. If after 1 hour the blood glucose level is more than 7.8 mmol/L (140 mg/dL), it is followed by a 100 g glucose dose. The diagnosis of gestational diabetes is then defined by a blood glucose level meeting or exceeding the cutoff values on at least two intervals, with cutoffs as follows: Before glucose intake (fasting): 5.3 mmol/L (95 mg/dL) 1 hour after drinking the glucose solution: 10.0 mmol/L (180 mg/dL) 2 hours: 8.6 mmol/L (155 mg/dL) 3 hours: 7.8 mmol/L (140 mg/dL)

[Microalbuminuria in patients with glomerulonephritis in remission].

The authors focused their attention on residual changes in patients with glomerulonephritis who have a zero or only "physiological" proteinuria (under 0.15 g/24 hours), normal or slightly elevated s-creatinine and who do not suffer from hypertension. In these patients microalbuminuria in urine per 24 hours was assessed. Patients with albuminuria under 20 micrograms/min were included in the group with normal albuminuria (13 patients) and patients with albuminuria of more than 20 micrograms/min in the microalbuminuric group (11 patients). The two groups did not differ significantly as to age, sex, duration of the disease, maximum levels of proteinuria and s-creatinine values at the onset of the disease. S-creatinine and blood pressure values at the time of investigation were also comparable. The groups differed, however, significantly as to the period of "absolute" remission which the authors defined as the period during which proteinuria did not exceed the "physiological" limit. This period was in the normoalbuminuric group significantly longer--on average 5.1 years--while in the microalbuminuric group it was 2.1 years (difference at the 1% level of significance).

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)

Minimal Change Disease -- Evaluation -- Basic labs:

Urine collection: A spot protein/creatinine ratio greater than 200 mg/mmol in children and protein/creatinine ratio>300-350mg/mmol in adults is consistent with nephrotic syndrome, as is a 24-hour urine collection that reveals a total protein greater than 3 to 3.5 g/24hour in adults. A report of measuring protein output as gms/m2/hr accounts for differences in body mass. A measurement of 40mg/m2/hour or greater (1gm/m2/24hour) is indicative of proteinuria consistent with nephrotic syndrome in children. Microscopic hematuria is present in 10% to 30% of adults. [13]

Gestational diabetes

The test involves drinking a solution containing a certain amount of glucose, usually 75 g or 100 g, and drawing blood to measure glucose levels at the start and on set time intervals thereafter. The diagnostic criteria from the National Diabetes Data Group (NDDG) have been used most often, but some centers rely on the Carpenter and Coustan criteria, which set the cutoff for normal at lower values. Compared with the NDDG criteria, the Carpenter and Coustan criteria lead to a diagnosis of gestational diabetes in 54 percent more pregnant women, with an increased cost and no compelling evidence of improved perinatal outcomes. The following are the values which the American Diabetes Association considers to be abnormal during the 100 g of glucose OGTT: Fasting blood glucose level ≥95 mg/dL (5.33 mmol/L) 1 hour blood glucose level ≥180 mg/dL (10 mmol/L) 2 hour blood glucose level ≥155 mg/dL (8.6 mmol/L) 3 hour blood glucose level ≥140 mg/dL (7.8 mmol/L)

The Neglected Significance of Glomerular Density as a 5-year Progression Indicator for IgA Nephropathy<sup>△</sup>.

Objective To investigate whether glomerular density (GD) could be an independent prognostic factor for patients of IgA nephropathy with estimated glomerular filtration rate (eGFR) of 30 to 60 ml/min per 1.73 m<sup2</sup, or for patients with time-average proteinuria < 0.5 g/d. Methods A total of 173 patients with biopsy-confirmed IgA nephropathy diagnosed from January 2000 to December 2010 were included. All of these patients were followed up for more than 5 years. The endpoint was a > 30% of decline in eGFR from baseline after 5-year follow-up. The optimal cut-off value of GD was calculated by ROC curve. Kaplan-Meier method and Cox regression analysis was used for survival analysis. Results A 30% of decline in eGFR occurred in 14.5% of all patients. The optimal diagnostic cut-off value of GD was 1.99/mm<sup2</sup (AUC = 0.90, sensitivity = 84.0%, specificity = 81.8%) determined by ROC curve. The low GD group (GD < 1.99 per mm<sup2</sup) experienced a significant increase in renal endpoint for patients with eGFR of 30 to 60 ml/min per 1.73 m<sup2</sup (six patients in lower GD group, while one patient in the other group). For patients with time-average proteinuria < 0.5 g/d, the lower GD group showed a higher eGFR decline from baseline (4.5±16.7 ml/min per 1.73 m<sup2</sup vs. -8.1±21.4 ml/min per 1.73 m<sup2</sup, P = 0.038); two patients in this group reached the endpoint, while no patients in the higher GD group did. Conclusion GD could be an independent prognostic factor for patients of IgA nephropathy with eGFR at 30 to 60 ml/min per 1.73 m<sup2</sup of body surface, particularly for those with time-averaged amount of urine protein less than 0.5 g per day.

Acute pancreatitis

At admission age in years > 55 years white blood cell count > 16000 cells/mm3 blood glucose > 11.1 mmol/L (> 200 mg/dL) serum AST > 250 IU/L serum LDH > 350 IU/L At 48 hours Calcium (serum calcium < 2.0 mmol/L (< 8.0 mg/dL) Hematocrit fall >10% Oxygen (hypoxemia PO2 < 60 mmHg) BUN increased by 1.8 or more mmol/L (5 or more mg/dL) after IV fluid hydration Base deficit (negative base excess) > 4 mEq/L Sequestration of fluids > 6 L The criteria for point assignment is that a certain breakpoint be met at any time during that 48 hour period, so that in some situations it can be calculated shortly after admission. It is applicable to both gallstone and alcoholic pancreatitis. Alternatively, pancreatitis can be diagnosed by meeting any of the following:[2] Alternative Ranson score Ranson's score of ≥ 8 Organ failure Substantial pancreatic necrosis (at least 30% glandular necrosis according to contrast-enhanced CT)

[Frequency of diagnosis and clinic presentation of glomerulopathies in Uruguay].

The Uruguayan Registry of Glomerulopathies began its activity in 1974 and since 1985 is a national registry. The aim of this report is to analyze the incidence and the variations in frequencies of the histological diagnosis and clinical presentation during the 1980-2003 period. From the 2,058 patients with renal biopsy in the whole period, we analyzed the histological diagnosis and the following data has been collected when the patients were registered: age, gender, clinical syndrome, proteinuria, hematuria, serum creatinine, blood pressure and time from the first symptom. Four periods of registry entry were considered: 1980-1989, 1990-1994, 1995-1999 and 2000-2003. Chi-square and Student test for independent samples were used to evaluate the differences among the variables frequencies in the four periods. The incidence of registered glomerulopathies per million population (pmp) increased from 13 (1980-1989) to 43 (2000-2003). In the 2000-2003 period, the incidences pmp were: primary glomerulopathy (PG), 25.3 and secondary glomerulopathy, 14.2. The highest incidences pmp were: focal and segmental glomeruloesclerosis (FSGS) 6.4; vasculitis 5.4; lupus nephritis 4.6; minimal change disease (MCD) 4.6; IgA nephropathy (IgAN) 4.5; and membranous nephropathy (MN) 4.0. The most frequent PG were the FSGS (29.3%) and the MCID (19.6%). The FSGS frequency decreased from 36.3% in 1995-1999 to 19.1% in 2000-2003. The IgAN frequency increased from 5.2% in 1980-1989 to 17.5% in 2000-2003. Nephrotic syndrome was the most frequent clinical presentation; its frequency was over 30% in the four periods. Asymptomatic urinary abnormality frequency increased from 14.0% in 1980-1989 to 22.7% in 2000-2003. The frequency of serum creatinine under 1.5 mg/dl, increased from 42.2% in 1980-1989 to 67.2% in 2000-2003 (p = 0.001). The frequency of serum creatinine over 6.0 mg/dl, decreased from 19.3% in 1990-1994 to 7.2% in 2000-2003. The percentage of patients referred since the first month of the apparent onset of the disease increased from 24.0% in 1980-1989 to 40.1% in 2000-2003 (p < 0.001). In Uruguay, the incidence of glomerulopathies with histological diagnosis has increased and the frequency of the different types has changed. Several indicators seem to show that the reference of patients to the nephrologist tended to be earlier in the last years.

Long-term beneficial effects of angiotensin-converting enzyme inhibition in patients with nephrotic proteinuria.

Angiotensin-converting enzyme inhibitors (ACEI) can reduce proteinuria in diabetic and nondiabetic nephropathy. However, no studies have determined whether this antiproteinuric effect modifies the progression of renal insufficiency. We studied the evolution of 46 nondiabetic patients with nephrotic proteinuria treated with captopril for a minimum of 12 months. The follow-up period before captopril treatment was 12 to 18 months. At the end of follow-up, after captopril introduction (24.4 +/- 7.6 months), proteinuria had decreased from 6.3 +/- 2.5 to 3.9 +/- 3.1 g/24 h (P less than 0.001), with a mean decrease of 45% +/- 28%. The proteinuria decrease was higher in patients with reflux nephropathy, proteinuria associated with reduction of renal mass, inactive crescentic glomerulonephritis, nephroangiosclerosis, and IgA nephropathy, whereas patients with membranous glomerulonephritis and idiopathic focal glomerulosclerosis showed a poorer response. Patients were separated according to a proteinuria reduction greater (group A, 23 patients) or lower (group B, 23 patients) than 45% of the initial value. At the end of follow-up, renal function had not significantly changed in group A with respect to values at the start of treatment: serum creatinine (SCr) was 229 +/- 167 mumol/L (2.6 +/- 1.9 mg/dL) versus 203 +/- 97 mumol/L (2.3 +/- 1.1 mg/dL), and creatinine clearance (CrCl) was 0.80 +/- 0.52 mL/s (48 +/- 31 mL/min) versus 0.87 +/- 0.47 mL/s (52 +/- 28 mL/min). The slope of the reciprocal of Scr (1/SCr) showed a significantly beneficial change after captopril introduction.(ABSTRACT TRUNCATED AT 250 WORDS)

One-center experience with cyclosporine in refractory nephrotic syndrome in children.

Uncontrolled or refractory nephrotic syndrome (NS), seen in a variety of glomerular disorders, leads to end-stage renal disease (ESRD). This study describes the use and efficacy of cyclosporine (CSA) for the treatment of refractory NS in 83 children seen over a 10-year period. The histological diagnosis leading to the NS was focal segmental glomerulosclerosis (FSGS) in 51% (n = 42), IgM nephropathy in 20% (n = 17), membranoproliferative glomerulonephritis in 10% (n = 8), lupus nephritis in 6% (n = 5), human immunodeficiency virus (HIV) nephropathy in 5% (n = 4), minimal change disease in 7% (n = 6), and membranous nephropathy in 1% (n = 1) of patients. During CSA therapy the mean proteinuria of the study population decreased from 5.14 g/24 h (4.80 g/m2 per 24 h) to 1.23 g/24 h (0.92 g/m2 per 24 h) (P < 0.001), the mean serum albumin increased from 2.13 g/dl to 3.53 g/dl (P < 0.001), the mean serum cholesterol decreased from 364 mg/dl to 223 mg/dl (P < 0.001), and the mean serum creatinine increased from 0.77 mg/dl to 1.2 mg/dl (P < 0.01). When analyzed by histological diagnosis, similar significant trends of reduction in proteinuria were seen in all but the lupus group. There was a rise in serum creatinine following the use of CSA in patients with FSGS, lupus nephritis, and HIV nephropathy; however the elevated serum creatinine was only significant in patients with FSGS. At the end of the study period, 20 patients had reached ESRD, of which 11 had FSGS, 5 had lupus nephritis, and 4 were patients with HIV nephropathy. Fifty-four patients were in remission at the end of the study period (48 with proteinuria < 100 mg/24 h and 6 with proteinuria < 500 mg/24 h). In conclusion, among children with refractory NS, CSA induced a remission in a large proportion. However toxicity, as noted by the rise in serum creatinine, was observed in several patients. Since this toxicity may be drug induced or a natural progression of the disease, careful monitoring and close follow-up are essential.

Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases.

IgA nephropathy (IgAN) may present with a wide variety of histologic patterns on renal biopsy, ranging from a minimal lesion to a diffuse proliferative glomerulonephritis (GN). The histologic features of 244 cases of IgAN (not including Schönlein-Hanoch nephritis) diagnosed between 1980 and 1994 were reviewed, and each case was subclassified using the following, relatively simple histologic classification scheme: subclass I (39 cases): minimal or no mesangial hypercellularity, without glomerular sclerosis; subclass II (18 cases): focal and segmental glomerular sclerosis without active cellular proliferation; subclass III (110 cases): focal proliferative GN; and subclass IV (42 cases): diffuse proliferative GN; and subclass V (35 cases): any biopsy showing > or = 40% globally sclerotic glomeruli and/or > or = 40% estimated cortical tubular atrophy or loss. Subsequent analysis of renal survival in 109 patients who underwent biopsy before or during 1992 for whom such data were available showed a strong, statistically significant correlation between histologic subclass and renal survival, with an order I, II (greatest survival) > III > IV, V. Crescents were a significant negative prognostic indicator for renal survival in subclass III (but not in subclass IV), and interstitial expansion was a negative prognostic indicator in subclasses III and IV, although the statistical significance of these were not maintained after controlling for serum creatinine at the time of biopsy. The presence of peripheral glomerular capillary deposits ultrastructurally had no prognostic significance. With respect to clinical presentation, hypertension (systolic blood pressure > or = 130 mm Hg and diastolic blood pressure > or = 90 mm Hg) and proteinuria of > or = 2.0 g/24 hr were significant negative prognostic indicators for renal survival, even when controlling for serum creatinine at the time of renal biopsy. The presence of gross hematuria correlated significantly with increased renal survival by univariate analysis, but not when controlling for serum creatinine at the time of renal biopsy. The findings of this study confirm the wide variety of clinical and histopathologic presentations of IgAN, and indicate the utility of the proposed histologic classification schema in assessing a patient's likelihood of ultimately developing end-stage renal disease.

[A 91-year-old man with a stroke, hypertension, and renal failure].

We report a 91-year-old man who had a stroke and died of renal failure. He had been treated for hypertension since 20 years before the onset of the present illness. In addition, he was operated on a gastric cancer 17 years previously. Otherwise he was doing well until May 29, 1991 (when he was 87-year-old) when he had sudden onset of dysarthria and right facial weakness. He was admitted to our hospital. On admission, general physical examination was unremarkable, and neurologic examination revealed a mentally sound man with slight dysarthria, right facial weakness, orolingual dyskinesia, and dysequilibrium in which he showed difficulty in tandem gait; however, no cerebellar ataxia was noted. A cranial CT scan revealed leukoaraiosis with multiple low density areas in the cerebral white matter. His BUN was 37 mg/dl and Cr 2.2 mg/dl. His neurologic symptoms cleared within the next few weeks and he was discharged with ticlopidine 100 mg q.d.. He had been doing well after the discharge except for gradual worsening of his renal function; his BUN was 65 mg/dl and Cr 3.27 mg/dl in April of 1994. On March 10, 1995, he fell down and hit his back; he became unable to walk because of pain, and he was admitted again on March 16, 1995. On admission, his blood pressure was 170/80 mmHg. There was an 1 + pitting pretibial edema; otherwise general physical examination was unremarkable. Neurologic examination revealed an alert and oriented man, however, Hasegawa's dementia scale was 23/30. Higher cerebral functions as well as cranial nerves were intact. He showed some unsteadiness of gait, however, no motor weakness or ataxia was noted. Deep tendon reflexes were diminished, but Chaddock sign was positive bilaterally. Vibration was diminished in the feet, however, pain and touch sensations were intact. Laboratory examination revealed a compression fracture of the twelfth thoracic vertebra. Blood count and chemistries were as follows; Hb 7.6 g/dl, Hct 23.3%, TP 6.0 g/dl, Alb 3.6 g/dl, BUN 87 mg/dl, Cr 4.53 mg/dl, T-Chol 174 mg/dl, HDL-Chol 49 mg/dl, Glu 156 mg/dl, Na 142 mEq/L, K 5.4 mEq/L, Cl 115 mEq/L. A urine specimen contained 1 + protein and 1 + glucose, and the sediments contained hyaline casts. A cranial CT scan was essentially same as that taken four years ago. His hospital course was complicated with pneumonia, congestive heart failure, and progressive renal failure. He was treated with intravenous fluid, chemotherapy, and other supportive measures, however, he expired from respiratory failure on April 30, 1995. He was discussed in a neurologic CPC, and the chief discussant arrived at the conclusion that the patient had Binswanger's disease in the brain, benign nephrosclerosis from arteriolosclerosis due to hypertension, congestive heart failure, and pneumonia. Opinions were divided regarding the question as to whether or not this patient had Binswanger's disease. Although his cranial CT scan revealed leukoaraiosis, his dementia and gait disturbance was only mild until his fall on March, 1995. Clinical features did not conform to those of Binswanger's disease. Postmortem examination of the right hemisphere revealed wide spread atherosclerosis and arteriolosclerosis. The kidney showed benign nephrosclerosis due to arteriolosclerosis. Sclerotic changes were also seen in the coronary arteries and the left middle cerebral artery with 70% stenosis. Myelin stain showed diffuse myelin pallor of the cerebral white matters with scattered small infarcts. Arterioles in the white matter showed arteriolosclerosis. Small infarcts were also seen in the putamen and in the thalamus. This patient appeared to have had circulatory disturbance of the white matter which is the basic abnormality causing Binswanger's disease. However, white matter changes in this patient were not quite severe enough to make a pathologic diagnosis of Binswanger's disease.