Lipasuria in acute pancreatitis: result of tubular dysfunction?

Lipase, in contrast to amylase, is completely reabsorbed by the proximal tubules after glomerular filtration. Therefore, no lipase is detectable in the unconcentrated urine according to the current opinion. The handling of lipase (detected with an enzyme-immunoassay) by the kidney was investigated in comparison with creatinine, amylase, and beta-2-microglobulin by clearance studies in acute pancreatitis (n = 10), burn injury (n = 4), glomerular proteinuria (n = 8), and controls without evidence of pancreatic or renal diseases (n = 5). In initial stages of acute pancreatitis a measurable clearance of lipase (mean: 49.6 microliters/min, range: 0.5-234) was found in association with corresponding increased clearances of beta-2-microglobulin (mean: 10.5 ml/min, range: 0.02-58.9) and of amylase (mean: 8.9 ml/min, range: 2.4-22.6) in nine of ten patients. This finding is consistent with a defect of tubular function. However, regression analysis failed to show a significant correlation between lipase and beta-2-microglobulin clearance. Repeated measurements during the course of pancreatitis in seven patients showed reversibility of tubular dysfunction. In patients with burn injury a similar elevation of clearances of beta-2-microglobulin and of amylase was found, but tubular dysfunction in this condition was not associated with lipasuria. In glomerular proteinuria a lipase clearance was found in two of five cases with moderate, and in the other three cases with severe impairment of creatinine clearance. beta-2-microglobulin clearance was normal in the former and only slightly elevated in the latter group. In conclusion lipase is measurable in the urine of most patients with acute pancreatitis as a result of a reversible tubular dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Osteomalacia secondary to renal tubular acidosis in a patient with primary Sj?gren's syndrome.

We report a case of a 41-year-old woman whose disease manifested as osteomalacia and whose etiological investigation revealed renal tubular acidosis secondary to primary Sj?gren's syndrome. Proximal tubular dysfunction was also present and was documented by increased urinary excretion of beta-2-microglobulin and retinol-binding protein. The patient showed clinical and laboratory improvement after treatment with oral potassium citrate, calcium supplements and steroids.     

Nephropathy associated with sickle cell anemia: an autologous immune complex nephritis. II. Clinicopathologic study of seven patients.

A variety of renal structural and functional abnormalities have been associated with sickle cell disease. To define the relationship between the hemoglobinopathy and glomerular disease, clinicopathologic correlations, renal morphologic, ultrastructural immunohistologic and functional studies were performed on seven patients with clinical and laboratory evidence of glomerular disease. In addition, immunologic studies including isolation and characterization of cryoprecipitable immune complexes, and determination of immunoglobulin, total complement and complement component levels, and antibody titers to several antigens were performed in an attempt to define the etiologic and pathogenic mechanisms of the renal disease and its relationship to sickle cell anemia. Proteinuria was presnet in all patients. The nephrotic syndrome, hypertension, hematuria and renal insufficiency were found in more than one half the patients. All patients had membranoproliferative glomerulonephritis of varying degree; glomerular basement membrane splitting, electron dense deposits in the glomerulus; interstitial fibrosis, tubular atrophy and hemosiderin deposits were frequent. Immunoglobulin complement components (classif complement pathway) and renal tubular epithelial antigen were distributed in a granular pattern along the glomerular basement membranes of all patients studied by these methods. Cyroprecipitable complexes of renal tubular epithelial antigen-antibody to renal tubular epithelial antigen as well as antibody to renal epithelial antigen were detected in the circulation of some patients. There was no serologic evidence of activation of the alternate complement pathway. These studies demonstrated an immune deposit normocomplementemic nephritis associated with sickle cell anemia; they further support our hypothesis that the relationship is more then coincidental, and is mediated by glomerular deposition of immune complexes of renal tubular epithelial antigen-antibody to renal tubular epithelial antigen, the antigen possibly released after tubular damage secondary to oxygenation and hemodynamic alterations related to sickle cell disease.     

Glomerular and tubular proteinuria as markers of nephropathy in rheumatoid arthritis.

OBJECTIVE: We examined the prevalence of nephropathy in unselected patients with rheumatoid arthritis (RA) by measurement of marker proteins for glomerular and tubular damage in urine. METHODS: A highly sensitive immunoluminometric assay was used to measure albumin, immunoglobulin G and alpha1-microglobulin in 24 h urines of 44 RA patients and a control group of 46 patients with generalized osteoarthritis (OA). RESULTS: Fifty-five per cent of RA patients were found to have proteinuria as a symptom of renal disease. Drug therapy or vasculitis were identified as possible reasons for proteinuria in only 25% of these patients; in most patients (75%), no reason for proteinuria was found. Tubular and mixed proteinuria were more frequent than glomerular proteinuria. Only 15% of the control group exhibited mild proteinuria, which was attributable to nephrotoxic factors. The renal function of RA patients and the control group did not differ significantly. CONCLUSIONS: Proteinuria is a frequent symptom of nephropathy in RA. Screening for renal disease in RA should not only include creatinine measurement and dipstick examination of urine, but also more sensitive methods to detect tubular and glomerular proteinuria as a marker of tubular and early stages of glomerular damage.     

Changes in urinary retinol binding protein excretion and other indices of renal tubular damage in patients with non-insulin dependent diabetes.

Changes in urine retinol binding protein (RBP, M(r) 21,000) excretion and other indices of renal tubular damage were investigated in the patients with non-insulin dependent diabetes mellitus (NIDDM). Changes in urine RBP excretion were well paralleled with those of urine NAG excretion. In RBP-negative patients, the subjects with hypertension (systolic blood pressure > or = 140 mmHg or diastolic blood pressure > or = 90 mmHg) showed higher beta 2-microglobulin (beta 2-MG) excretion and albumin (Alb)/Cr ratios than normotensive ones. In addition, both urine beta 2-MG excretions and Alb/Cr ratios were significantly increased in RBP-positive patients. The measurement of urine RBP excretion may have an additional role in the diagnosis of renal tubular dysfunction in diabetic patients.     

Further evidence for tubular dysfunction in insulin dependent diabetes

There is evidence that increased excretion of urinary enzymes and low-molecular mass proteins indicate impaired tubular function. The excretion of N-acetyl-beta-d-glucosaminidase (NAG), lysozyme, and ribonuclease in Type I diabetic patients with (n = 19) and without (n = 17) persistent proteinuria (urinary protein excretion > 0.5 g/day) was investigated and compared with this exretion in 30 weight- and gender-matched nondiabetic subjects without renal disease. Urinary NAG excretion was significantly higher in diabetic patients with and without persistent proteinuria (1.16 ± 0.09 and 3.19 ± 1.2 Umol/L creatinine, respectively) compared to controls (0.37 ± 0.03 Umol/L creatinine p < 0.01). In addition, the urinary excretion of lysozyme and ribonuclease was significantly increased in diabetic patients. Urinary NAG was found to correlate positively with albuminuria and proteinuria (r = 0.95 and 0.93, respectively), as well as with ribonuclease and lysozyme (r = 0.93 and 0.60; p < 0.01) in patients with persistent proteinuria. Furthermore, NAG excretion was significantly related to the duration of diabetes (r = 0.36; p < 0.05). No relationship existed between urinary NAG and serum creatinine, beta-2-microglobulin, and degree of metabolic control (HbA₇). The lysozyme excretion, but not NAG excretion, was significantly related to hypertension in patients with clinical proteinuria. In conclusion, our results suggest a relationship between the development of tubular dysfunction and the impairment of glomerular function in diabetic nephropathy. An increased excretion of NAG and low-moecular mass proteins may indicate early nephropathy.     

Renal tubular dysfunction in patients with inflammatory bowel disease treated with aminosalicylate.

BACKGROUND: An increasing number of case reports indicate potential nephrotoxicity of 5-aminosalicylic acid (5-ASA), which shares similarities with the chemical structures of both phenacetin and acetylsalicylic acid. AIM: In a point prevalence study the occurrence of sensitive indices indicative of early kidney malfunction was assessed in outpatients with inflammatory bowel disease. METHODS: Routine indices of kidney function (creatinine clearance, urinary protein content, pH, electrolytes, and microscopy) were investigated in 223 patients with inflammatory bowel disease as well as sensitive markers of glomerular or tubular dysfunction (microproteinuria by SDS polyacrylamide gel electrophoresis (SDS-PAGE), urinary concentrations of N-acetyl-beta-D-glucosaminidase, alpha 1-microglobulin, gamma-glutamyltransferase (GGT), alkaline phosphatase (AP), and albumin). Histories of exposure to 5-ASA were assessed by questionnaire. RESULTS: Patients receiving high amounts of 5-ASA, both actual as well as on a lifetime basis, showed an increased prevalence of tubular proteinuria by SDS-PAGE. Raised values for urinary AP and GGT indicate proximal tubular epithelial cells as the source. All other kidney function tests were normal. Analysis of covariates indicated strong associations between disease activity and size of 5-ASA doses as well as alterations in kidney tubular function. CONCLUSION: The possibility exists that high doses of 5-ASA may be associated with proximal tubular proteinuria. This point prevalence study cannot dissect the possible impact of chronic inflammation from high dose 5-ASA treatment and further prospective studies are warranted.     

Urinary albumin and beta 2-microglobulin excretion rates in patients with systemic lupus erythematosus

The daily urinary albumin and beta 2-microglobulin excretion rates were measured with sensitive radioimmunoassays in 14 patients with systemic lupus erythematosus (SLE). The duration of SLE ranged from 0.5 to 18 years, mean 10 years. The mean age was 37 years. All patients except 5 received prednisone, 5-20 mg/day. None of the patients had proteinuria as judged by the "Albustix" test, and all had normal serum creatinine. The daily urinary albumin and beta 2-microglobulin excretion rates were nearly the same as those previously found by us in 27 adult control subjects with a mean age of 44 years. Our study shows that SLE patients without clinical proteinuria have a completely normal renal glomerular and tubular protein handling, irrespective of the duration of the disease.     

The morphology of "acute tubular necrosis" in man: analysis of 57 renal biopsies and a comparison with the glycerol model.

Renal biopsies from 24 patients with oliguric "acute tubular necrosis" (ATN) and 26 patients with non-oliguric ATN were compared with biopsies from 7 patients who had recently recovered from ATN and 20 control patients. Many morphologic changes were present in the biopsies of patients with ATN and absent in controls, but only two lesions were significantly more severe in patients who had ATN at the time of the biopsy compared with patients who had recently recovered from ATN. These two lesions, necrosis of individual tubular epithelial cells and loss of brush border in proximal tubules, may play a role in the pathogenesis of renal functional failure in ATN. Necrosis of individual tubular epithelial cells appeared to be a continuing process. In the patients with non-oliguric acute renal failure there was a positive correlation between duration of renal failure and severity of tubular necrosis. This was not observed in the patients with oliguric acute renal failure, but otherwise there were no identifiable morphologic differences between the two groups. The glycerol model of acute renal failure in the rabbit was found to differ in several significant ways from ATN in man. Despite the fact that the rabbits had significantly less severe renal failure, their kidneys showed much more severe tubular necrosis and much more prominent presence of tubular casts than was the case in biopsies from patients with ATN. Loss of brush border in proximal tubules was not an important feature of the glycerol model of acute renal failure in the rabbit. We suggest that the glycerol model is not analogous to human ATN and may have an entirely different pathogenesis.     

Hypophosphatemia and renal tubular dysfunction in alcoholics. Are they related to liver function impairment?

The study was designed to evaluate (a) the role of reduced renal phosphate reabsorptive capacity assessed as the ratio of maximum capacity for renal phosphate reabsorption (TmPO4) to glomerular filtration rate (GFR) in the pathogenesis of hypophosphatemia in alcoholics, (b) possible mechanisms leading to reduced TmPO4/GFR, and (c) the effect of liver function impairment on TmPO4/GFR. The TmPO4/GFR, its major extrarenal determinants, ratios of urinary excretion gamma-glutamyl transpeptidase and of alpha-glucosidase to GFR (uGGT/GFR and uAGL/GFR), indices of structural damage of renal tubular cells, and fractional clearance of lysozyme, an index of proximal renal function, were evaluated in 31 alcoholics with alcohol-related liver disease, 24 alcoholics without alcohol-related liver disease, 14 patients with non-alcohol-related liver disease, and 25 control subjects. Hypophosphatemia was found in 35% of alcoholics with alcohol-related liver disease, 29% of alcoholics without alcohol-related liver disease, and no patients with non-alcohol-related liver disease. A reduced TmPO4/GFR was the major determinant of hypophosphatemia in both groups of alcoholics. No difference in extrarenal determinants of TmPO4/GFR was found between alcoholics with and without hypophosphatemia. Alcoholics with and without alcohol-related liver disease had increased uGGT/GFR and normal uAGL/GFR regardless of serum phosphate level. Fractional clearance of lysozyme, instead, was increased only in hypophosphatemic alcoholics with and without alcohol-related liver disease. The TmPO4/GFR correlated inversely with the fractional clearance of lysozyme in both groups of alcoholics (P less than 0.01). The TmPO4/GFR and urinary enzymes were normal in patients with non-alcohol-related liver disease. It was concluded that a reduced TmPO4/GFR is involved in the pathogenesis of hypophosphatemia in alcoholics. A proximal tubular dysfunction seems to be responsible for the reduced TmPO4/GFR. Liver function impairment is not required for the expression of this tubular dysfunction.     

Demonstration of β2-Microglobulin in the Kidney by Direct Immunofluorescent Staining

Direct immunofluorescent staining with fluorescein isothiocyanate conjugated goat anti-human beta 2-microglobulin (beta 2M) was used to determine the localization of beta 2M in kidney tissue, obtained by biopsies or nephrectomies for various renal diseases. beta 2M was found in the renal tubular epithelial cell cytoplasm and occasionally in the tubular basement membranes in 48 out of 79 pathologic specimens tested, but not in 3 normals. beta 2M was seen in the tubular cells in all cases of primary tubulointerstitial disease and in all cases with secondary tubular damage associated with glomerular disease or systemic disease. This supports the concept that beta 2M is metabolized in proximal tubular epithelial cells, and its deposition indicates impairment of tubular handling.     

Partially reversible renal tubular damage in patients with obstructive jaundice

Decreased serum uric acid levels resulting from renal urate wasting have been occasionally encountered in jaundiced patients. However, in these cases, there are no data concerning the underlying renal tubular defects. In the present study, we investigated the renal tubular function in 35 patients with obstructive jaundice of various severity and causes (11 with lithiasis, 17 with carcinoma, and 7 with intrahepatic cholestasis). A detailed study of the renal tubular function was performed. Beyond the conventional methods, (1)H-NMR spectroscopy of urine was used to evaluate noninvasively renal damage by the characteristic perturbation in the excretion pattern of low-molecular weight endogenous metabolites. On admission, patients with obstructive jaundice had significantly lower serum uric acid and phosphate levels and higher bile acid concentrations compared with 40 age- and sex-matched controls. Serum uric acid levels presented a negative correlation with the total and direct bilirubin as well as the fractional excretion of uric acid. Furthermore, a great number of the patients studied developed one or more proximal tubular dysfunction manifestations beyond uricosuria, such as renal glucosuria, phosphaturia, and increased excretion of alpha(1)-microglobulin. (1)H-NMR spectroscopy of the urine showed decreased levels of citrate and hippurate and increased levels of 3-hydroxybutyrate and acetate. In 12 patients partial or complete remission of jaundice was followed by an improvement of the proximal renal tubular damage. In conclusion, obstructive jaundice can cause a partially reversible generalized proximal tubular dysfunction.     

N-acetyl-beta-glucosaminidase and beta 2-microglobulin. Their urinary excretion in patients with renal parenchymal disease

The urinary excretion of N-acetyl-beta-glucosaminidase (NAG) and beta 2-microglobulin (beta 2M) was studied in 43 patients with various forms of renal parenchymal disease. Patients with membranous nephropathy, membranoproliferative glomerulonephritis, focal segmental glomerulosclerosis, obstructive pyelonephritis, nephrosclerosis, and minimal change nephropathy generally had urinary NAG and beta 2M levels more than 3 SDs above those seen in normal subjects. Patients with progressive renal disease averaged higher NAG and beta 2M urinary levels than those with the same renal lesion and stable function. Since elevated urinary levels of NAG and beta 2M suggest renal tubular injury or dysfunction, our observations suggest tubulointerstitial involvement in a wide variety of renal diseases.     

Glomerular filtration rate and tubular involvement during acute disease and convalescence in patients with nephropathia epidemica

Glomerular filtration rate (GFR) and tubular involvement were studied in 74 patients with serologically verified nephropathia epidemica (NE). Increased levels of serum creatinine and serum beta 2-microglobulin were documented in 96% and 99% of the patients, respectively. The mean of the lowest estimated GFR was 26 ml/min. Proximal tubular reabsorptive capacity was assessed by urinary loss of beta 2-microglobulin and cell damage by urinary activity of N-acetyl-beta-D-glucosaminidase. Both of these parameters were elevated in most of the patients during the acute phase of the disease. Increased serum levels of Tamm-Horsfall-specific IgG and/or IgA occurred in 72 of 74 patients. No patient required dialysis and there was no mortality. Six months after discharge only three patients had a GFR less than 80 ml/min as estimated by [51Cr]EDTA clearance; two of these had underlying chronic diseases and one had suffered clinically severe NE. Desmopressin tests showed decreased urine osmolarity in three patients 8 months after discharge. These three had chronic diseases, which may have contributed to the impaired tubular function. Thus, there was a markedly decreased GFR and a tubular dysfunction in the acute phase of NE. Most patients recovered within a few months and none showed evidence of chronically impaired renal function due to NE.     

Renal disease in chronic arthritis of childhood. A study of urinary N-acetyl-beta-glucosaminidase and beta 2-microglobulin excretion

Urinalyses of randomly obtained samples from children with various types of chronic arthritis revealed proteinuria in 2.3% of patients, hemoglobinuria in 3.5%, erythrocyturia in 4.1%, and leukocyturia in 5.3%; these frequencies are within the range found by screening school children. However, raised urinary levels of N-acetyl-beta-glucosaminidase and/or beta 2-microglobulin (both sensitive measures of renal tubular damage) were found more frequently in children with chronic arthritis than in controls (P less than 0.0001). Abnormalities of either N-acetyl-beta-glucosaminidase or beta 2-microglobulin excretion were associated with active arthritis as measured by physician global estimate of disease activity, with a polyarticular onset of juvenile rheumatoid arthritis, and with the use of slow-acting antirheumatic drugs or the concurrent use of more than 1 nonsteroidal antiinflamtory drug. Abnormal renal tubular function appears to be common in chronic arthritis of childhood. The long-term consequences of this abnormality remain to be elucidated.     

Renal tubular proteinuria in patients with irritable bowel syndrome

OBJECTIVE: Irritable bowel syndrome (IBS) is a common condition that is poorly understood. We have previously demonstrated tubular protinuria in patients with inflammatory bowel disease. This study examined whether tubular proteinuria was a feature of IBS. METHODS: Eighty control subjects (male:female, 28:52; age range 20-65 years) and 21 patients with IBS (male:female, 9:12; age range 16-64 years) (not significant) were recruited. Patients with known renal disease, hypertension, diabetes or microbiological evidence of urinary infection were excluded. The IBS patients all fulfilled the ROME II criteria. None had preceding gastroenteritis. Urinary alpha1-microglobulin (alpha1-M) was measured in a second-voided morning urine sample and corrected for urinary concentration by measurement of creatine. Blood samples were analysed for haematochemical indices including C-reactive protein. Statistical analysis was by unpaired t test. RESULTS: None of the IBS patients were reclassified with inflammatory bowel disease over a 5-year follow up period. All had normal haematochemical parameters. Mean +/- standard deviation urinary alpha1-M concentrations were significantly higher in IBS patients than controls (IBS patients, 1.17 +/- 0.65 mg/mmol; controls, 0.75 +/- 0.36 mg/mmol; P < 0.01) and exceeded 1.5 mg/mmol (the upper reference limit) in seven patients. There was no difference in urinary alpha1-M concentrations in the diarrhoea-predominant and constipation-predominant groups (mean +/- standard deviation, 1.342 +/- 0.65 versus 0.76 +/- 0.48 mg/mmol; P = 0.062). CONCLUSIONS: Urinary alpha1-M concentration is commonly increased in IBS, suggesting the presence of renal proximal tubular injury.     

p38-MAPK inhibition and endotoxin induced tubular dysfunction in men

BACKGROUND: To evaluate the possibility of preventing endotoxin induced renal damage by p38-MAPK inhibition in a human model. DESIGN AND METHODS: Twenty-one healthy young male volunteers received 4 ng/kg Escherichia coli endotoxin as a single dose. Four groups of volunteers received an oral dose of placebo or 350, 700 or 1400 mg RWJ-67657, a p38-MAPK inhibitor, 20 min before endotoxin infusion. Urine samples were collected at set time intervals. The urinary excretion rate of beta(2)-microglobulin and N-acetyl-beta-D-glucosaminidase, as indicators of tubular dysfunction was determined. RESULTS: There was a significant increase of beta(2)-microglobulin and N-acetyl-beta-D-glucosaminidase urine excretion rate after endotoxin infusion in the placebo group. p38-MAPK inhibition prevented the increase of markers for tubulopathy. CONCLUSIONS: Endotoxin infusion induces measurable tubular damage. Blocking the p38-MAPK may prevent this damage. The mechanism is unclear, but blocking TNF-alpha release is a possible explanation.     

Nephropathy associated with sickle cell anemia: an autologous immune complex nephritis. I. Studies on nature of glomerular-bound antibody and antigen identification in a patient with sickle cell disease and immune deposit glomerulonephritis.

The nature of the glomerular-bound antibody and the putative antigen was investigated in one of the patients with sickle cell disease and immune deposit membranoproliferative glomerulonephritis by immunohistologic and glomerular antibody elution. Renal proximal tubular epithelial antigen was localized in association with immunoglobulins G (IgG), M (IgM), Clq fraction of the first component of complement (Clq) and the third component of complement (C3) in a granular pattern along the glomerular basement membrane of the patient's kidney. IgG and IgM were eluted from glomeruli. These immunoglobulins fixed to the proximal tubules of normal human kidney by direct immunofluorescence. This localization was abolished by absorption of the eluted immunoglobulins with renal tubular epithelial (RTE) antigen. The IgG eluted from the glomeruli blocked the fixation of rabbit anti-RTE antigen to normal proximal tubular brush border. These studies suggest that the nephritis in this patient was due to deposition of complexes or RTE antigen and specific antibody. An autologous immune complex nephritis may develop in some patients with sickle cell anemia secondary to RTE antigen released possibly after renal ischemia or some other phenomenon causing renal tubular damage.     

Urinary protein excretion patterns in reactive (secondary) systemic amyloidosis

Summary The urinary excretion of immunoglobulin light chains kappa and lambda, immunoglobulin G, transferrin, and beta-2-microglobulin was studied in 21 patients with nonimmunoglobulin-related amyloid nephropathy (secondary, type AA) associated with rheumatic disease and in 39 patients with glomerulopathy of nonamyloid origin, as well as in 22 patients with rheumatic disease without signs of nephropathy and in 15 healthy subjects. Patients with amyloidosis were found to have a higher ratio of excreted lambda/kappa light chains than patients with diabetic nephropathy or chronic glomerulonephritis. The increased lambda/kappa ratio was not dependent on the grade of proteinuria and was evident in patients with mild as well as heavy proteinuria. The ratio of lambda/kappa light chains in serum of patients with amyloidosis did not differ from that in healthy controls. The results suggest that amyloid deposition in the kidneys is associated with a selective alternation of the immunoglobulin light chain excretion in the urine.     

Medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome

ABSTRACT: BACKGROUND: Medullary nephrocalcinosis and distal renal tubular acidosis are closely associated and each can lead to the other. These clinical entities are rare in patients with nephrotic syndrome and polycythaemia is an unusual finding in such patients. We describe a patient with medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome due to minimal change disease. Proposed mechanisms of polycythaemia in patients with nephrotic syndrome and distal renal tubular acidosis include increased erythropoietin production and secretion of interleukin 8 which in turn stimulate erythropoiesis. CASE PRESENTATION: A 22 year old Sri Lankan Sinhala male with nephrotic syndrome due to minimal change disease was investigated for incidentally detected polycythaemia. Investigations revealed the presence of renal tubular acidosis type I and medullary nephrocalcinosis. Despite extensive investigation, a definite cause for polycythaemia was not found in this patient. Treatment with potassium and bicarbonate supplementation with potassium citrate led to correction of acidosis thereby avoiding the progression of nephrocalcinosis and harmful effects of chronic acidosis. CONCLUSION: The constellation of clinical and biochemical findings in this patient is unique but the pathogenesis of erythrocytosis is not clearly explained. The proposed mechanisms for erythrocytosis in other patients with proteinuria include increased erythropoietin secretion due to renal hypoxia and increased secretion of interleukin 8 from the kidney. This case illustrates that there may exist hitherto unknown connections between tubular and glomerular dysfunction in patients with nephrotic syndrome.