IgG subclass/IgM ratio and response to therapy in focal segmental glomerulonecrosis

Focal segmental glomerulosclerosis (FSGS) is relatively steroid resistant and no clinical or histological marker can predict the response to therapy. To investigate the role of serum immunoglobulin subclass/IgM in predicting the response to therapy in FSGS, serum concentrations of total IgG, IgG subclasses, and the ratio of serum IgG subclasses to total IgG (% IgG subclass) were measured in 27 children during the acute nephrotic state. Prednisolone, cyclophosphamide, and Persantine (dipyridamole) were given for 12 weeks. We divided the patients into good responders or poor responders according to clinical response. The clinical and nephrotic status were similar in both groups. Fourteen patients were good responders with higher serum IgGI/IgM than that of non-responders (4.00+/-0.67 vs. 1.61+/-0.20, P<0.05). There was no significant difference in IgG2/IgM between these two groups. These results suggest that higher serum IgGI/IgM ratios may be associated with a better clinical response. These changes may reflect dysregulation of immunoglobulin class switching in patients with FSGS.     

Plasma immunadsorption treatment in patients with primary focal and segmental glomerulosclerosis

BACKGROUND: In primary focal and segmental glomerulosclerosis (FSGS) renal prognosis is poor if no remission of proteinuria can be obtained by treatment. In some patients a permeability factor, responsible for damaging the glomerular epithelial cell and detectable by an in vitro test (GVV-test), seems to be present in the serum. METHOD: We determined the effects of an immunadsorption treatment (IAT) on proteinuria and glomerular permselectivity (using a neutral dextran and dextransulfate-sieving technique to assess glomerular size and charge selectivity) in five patients with FSGS in the native kidneys and three patients with recurrence of FSGS after kidney transplantation. Furthermore, we performed the GVV-test using sera obtained from the patients before and after therapy. RESULTS: IAT reduced proteinuria by more than 50% in four patients, all of whom had an improvement in glomerular-size selectivity. Charge selectivity was better preserved after therapy in three out of these four subjects. The GVV-test prior to IAT was positive in two patients who also responded clinically to therapy. After IAT the GVV-test was negative in all patients, indicating an elimination of the proteinuric factor in the two previously positive patients. CONCLUSION: We conclude that a positive GVV-test before treatment makes a favourable response of IAT on proteinuria likely in patients with FSGS. If a reduction of proteinuria can be obtained by IAT this is due to an improvement in glomerular size and/or charge selectivity.     

Age and ethnicity affect the risk and outcome of focal segmental glomerulosclerosis

In patients with proteinuria, African-American (AA) ethnicity is reported to be a risk factor for focal segmental glomerulosclereosis (FSGS) and its progression to end-stage renal disease (ESRD). We reviewed our single-center experience to determine the probability of FSGS and its progression to ESRD based on ethnicity and age at presentation in children with proteinuria with or without nephrotic syndrome. Proteinuria without systemic disease or acute glomerulonephritis was the presenting feature in 17% (236/1,403) of children in the renal patient database of Texas Children's Hospital, Baylor College of Medicine. Histopathological diagnoses were established in 107 of 236 patients (45%). FSGS was identified in 65 patients, accounting for 28% of all patients with proteinuria and 61% of patients who underwent renal biopsy. FSGS was more prevalent in AA (45%) than in non-AA patients (22%) (P=0.001), and AA patients with FSGS were older at presentation (12.7+/-4.4 years) than non-AA patients (5.6+/-4.6 years) (P<0.001). Among patients who underwent renal biopsy, increasing age at presentation increased the probability of having FSGS in AA but not non-AA patients (P=0.04). Five-year actuarial renal survival of FSGS was worse in AA (8%) than in non-AA patients (31%) (P=0.01). These data suggest an increased risk and worse outcome of FSGS in AA compared with non-AA children.     

Peritoneal protein loss in children with nephrotic syndrome during peritoneal dialysis

BACKGROUND: The passage of proteins across the glomerular filtration barrier is mainly determined by the size of the protein. In nephrotic syndrome (NS) the glomerular permselectivity is affected, causing proteinuria. Some authors suggest the existence of a generalized basement membrane defect. The permeability characteristics of the peritoneal basement membrane in children with NS are not known. METHODS: The transperitoneal transport of proteins with a different molecular weight (beta2-microglobulin MW 11800 D, albumin MW 69000 D, IgG MW 160000 D, and alpha2-macroglobulin MW 820000 D) was studied in a study group (group A) consisting of six stable nephrotic children (three with glomerulosclerosis and three with congenital nephrotic syndrome, one of them with mesangial sclerosis) and compared to a control group (group B) consisting of eight stable children on peritoneal dialysis. After a dwell of 6 h with Dianeal 1.36% dialysate and serum samples were collected. For each patient the dialysate to plasma (D/P) ratios of the four proteins were calculated. The D/P ratios of the nephrotic patients in group A were compared to the D/P ratios of the patients in the control group B. Data were expressed as mean +/- SD. RESULTS: The values for the D/P ratios (in percentage) of beta2-microglobulin, albumin, IgG and alpha2-macroglobulin in group A were 19.6+/-9.9, 2.7+/-1.7, 1.6+/-0.9, and 0.5+/-0.4, compared to 24.9+/-10.2, 4.0+/-2.3, 2.2 +/- 1.2, and 0.7 +/- 0.3 in the control group B. The ratios were plotted against MW on a double logarithmic scale. In all patients a linear relationship between molecular weight and D/P ratio of the proteins was obtained. The D/P ratios of the study group did not differ significantly from the control group. CONCLUSION: We conclude that the size selectivity of the capillary permeability is not affected in the peritoneal membrane in children with NS due to glomerulosclerosis and congenital nephrotic syndrome.     

Enhancement effect of an ethanol/Panasate 800 binary vehicle on anti-inflammatory drug permeation across excised hairless mouse skin

A total of 65 adult cases (53 males, 12 females) with biopsy-proven focal segmental glomerulosclerosis (FSGS) were studied. Hypertension, ascites and haematuria were seen in 13, 12 and 24 cases, respectively. Decreased creatinine clearance at presentation was found in 9 cases. Mean proteinuria per day, serum cholesterol and total protein were 7.5 +/- 4.3 g, 388.95 +/- 213.4 mg% (10.11 +/- 5.55 mmol/l) and 5.27 +/- 1.1 g% (0.527 +/- 0.11 milligram), respectively. Mesangial proliferation was seen in 13 cases and hilar sclerosis in 5. Fifty percent showed positive immunofluorescence; IgM in 10, C3 in 8, and IgG in 2. Forty-two cases could be followed (mean 32 months), out of which 38 had nephrotic syndrome and were treated with prednisolone; 58% showed response (31% complete remission and 27% partial remission). One patient in each group of responders and nonresponders had renal failure at the end of follow-up. Hypertension, degree of proteinuria, mesangial proliferation, degree of tubular atrophy and immunofluorescence findings did not significantly affect the response to steroids. We conclude that a group of patients with idiopathic adult FSGS has a favourable response to steroids, which cannot be predicted clinically.     

Changes of physico-chemical characteristics of red blood cells in children with nephrotic syndrome

Changes of milieu interieur in nephrotic syndrome (NS) have many consequences in various organs. We have measured the electrical charge of erythrocytes (Ery) with binding of alcian blue (AB) in 18 children with relapse of NS (12 minimal changes, 3 membranous and 3 mesangioproliferative glomerulonephritis) and 15 healthy children. The most important finding was that the binding of AB to Ery in patients with minimal change nephrotic syndrome (MCNS) and other aetiologies of NS was significantly less than that in the control group (p < 0.05). In addition, we have studied the thermal denaturation of the Ery membranes by differential scanning microcalorimetry. In some children with NS we have seen the splitting of B transition. We suppose that these phenomena occur as the result of structural change, which may involve lipoprotein components of the cytoskeletal network.     

Renal dopaminergic system in nephrotic syndrome and after remission

BACKGROUND: Although intrarenal dopamine is known to behave as an endogenous natriuretic hormone the role of the renal dopaminergic system in the sodium handling of nephrotic oedema remains unknown. STUDY DESIGN: We monitored the daily urinary excretion of free dopamine, L-DOPA-its precursor, and its metabolites, DOPAC and HVA, during sodium retention accompanying the nephrotic state and natriuresis leading to oedema mobilization in eight patients (mean age 8.0+/-2.4 years) with drug-induced remission of minimal-change nephrotic syndrome (MCNS). RESULTS: During natriuresis the urinary levels of dopamine did not increase in parallel with sodium excretion in any of the eight patients studied. Moreover, after remission of the nephrotic syndrome the urinary levels of dopamine were significantly lower than during the nephrotic state (1565.3+/-361.7 vs 2416.1+/-558.4, P= 0.02). In contrast, the urinary excretion of L-DOPA increased markedly during natriuresis resulting from remission of proteinuria (from 87.0+/-40.5 up to 296.9+/-86.3 nmol/24 h; P< 0.01). CONCLUSION: We conclude that the natriuretic response resulting from drug-induced remission of proteinuria in MCNS is accompanied by a decrease in the renal uptake/decarboxylation of L-DOPA to dopamine.     

Urinary fibrin-fibrinogen degradation products in nephrotic syndrome

The urinary concentration of fibrin-fibrinogen degradation products (F.D.P.) was measured in 90 patients with proteinuria above 2 g/1 and correlated with proteinuria, differential protein clearances, serum urea and creatinine, and renal biopsy findings. There was a linear correlation (r equals 0-7; P less than 0-001) between the urinary F.D.P. excretion and the selectivity of the proteinuria such that patients with highly selective proteinuria excreted only small amounts of F.D.P. whereas those with non-selective proteinuria excreted much higher levels. There was a significant correlation between the urinary F.D.P. excretion and the urine:serum (U:S) ratio of IgG excretion but not with the U:S ratio or urinary excretion of albumin or transferrin. Sephadex G200 column chromatography of the concentrated urine in 26 cases showed that patients with highly selective proteinuria excreted predominantly F.D.P. of low molecular weight in the urine whereas those with non-selective proteinuria excreted mainly fibrinogen and products of high molecular weight. Hence the type and quantity of F.D.P. in the urine are determined primarily by the differential filtration of fibrinogen and the various degradation products from the plasma through the glomerular basement membrane, which in turn is determined by the "pore size" of the basement membrane. In clinical nephrology measurement of the urinary F.D.P. level provides a rapid and convenient means of estimating the differential protein clearance.     

Value of fluorescence in situ hybridization for detecting the bcr/abl gene fusion in interphase cells of routine bone marrow specimens

A patient presented with a severe nephrotic syndrome and a renal biopsy consistent with early focal segmental glomerulosclerosis (FSGS). After a year of intensive immunosuppressive therapy proteinuria was unabated and renal function began to deteriorate. Treatment with weekly plasmapheresis combined with moderate doses of prednisone and azathioprine produced a dramatic decrease in proteinuria and serum creatinine. A marked fall in the B-cell population occurred during treatment, as well as an increase both in T-lymphocytes of the mature CD4+ helper/suppressor phenotype and in the immature/cytotoxic CD8+ phenotype. Activation of the immune system during treatment was demonstrated by an increase in the rate of spontaneous proliferation of peripheral blood mononuclear cells and an increase in T-cell expression of the interleukin-2 receptor.     

Transport of LDS-751 from the cytoplasmic leaflet of the plasma membrane by the rhodamine-123-selective site of P-glycoprotein

Hyperfibrinogenemia is a common feature of the nephrotic syndrome, and contributes to increased tendency for thrombosis and atherosclerosis. Its genesis is not certain, but the increase in liver fibrinogen mRNA in nephrotic rats indicates increased synthesis. Data in humans are scarce. We presently compared synthesis rates of fibrinogen and albumin in nephrotic adults (N = 7; plasma albumin 22.3 +/- 0.7 g/liter, proteinuria 12 g/day) and healthy control subjects (N = 8) using a primed/continuous infusion of the stable isotope L-[1-13C]valine for six hours. Absolute synthesis rate (ASR) of fibrinogen was 31 +/- 3 mg/kg/day in nephrotic subjects and 21 +/- 1 mg/kg/day in control subjects (P < 0.05), and positively correlated with plasma fibrinogen (P = 0.0317). The plasma fibrinogen pool was disproportionately increased in the nephrotic patients (271 +/- 30 mg/kg) compared to the controls (126 +/- 8 mg/kg), suggesting decreased fractional catabolic rate as well. The ASR of albumin was increased from 71 +/- 4 mg/kg/day in the controls to 160 +/- 19 mg/kg/day in the patients (P < 0.0001), and strongly correlated with the ASR of fibrinogen (P = 0.0046). Plasma alpha 2-macroglobulin was also elevated and correlated with the albumin synthesis rate, whereas plasma serum amyloid A and C-reactive protein were not elevated. These data suggest that in nephrotic patients the increased albumin synthesis is associated with an increase in synthesis of a specific and coordinated group of proteins, among which is fibrinogen.     

Hepatitis-B virus and schistosomiasis infections in childhood proteinuria

Hepatitis-B surface antigen (HBsAg), circulating anti-schistosomal IgG (CSAb) and circulating specific schistosomal immune complexes (CIC) were detected, using ELISA, in sera of 40 active nephrotic children, 40 active S. mansoni infected cases and 20 apparently normal age-matched controls. The presence of HBsAg cases was significantly higher among nephrotic cases (20%), active S. mansoni cases (17.5%) than controls. Moreover, HBsAg cases were significantly higher in positive CIC S. mansoni cases than negative CIC ones. The mean O.D. readings of CSAb was significantly higher in positive HBsAg nephrotic cases than negatives. At the same time, the anti-schistosomal antibodies were higher in S. mansoni cases with proteinuria than those without. Specific CIC level was significantly higher among nephrotic and schistosomiasis cases than controls. The CIC were significantly higher in schistosomiasis cases with positive HBsAg than those with negative HBsAg and were detected in 80% of cases with proteinuria compared to 37% of cases without proteinuria with a statistically significant difference. On the other hand, CIC level was not influenced, in nephrotic cases, by the presence or absence of HBsAg. It was concluded that the presence of proteinuria was considered as a good monitor of the kidney affection either with schistosomiasis or the nephrotic syndrome or the HBsAg. The detection of CIC can be used as a good monitor too and could be included in methods of early diagnosis and/or following the disease prognosis.     

Cyclosporine protects glomeruli from FSGS factor via an increase in glomerular cAMP

Cyclosporine (CsA) administration to patients with recurrent focal segmental glomerulosclerosis (FSGS) after transplantation results in remission of proteinuria. We have shown that sera from patients with recurrent FSGS can increase the glomerular albumin permeability (Palbumin) and that increase in glomerular cAMP levels can alter the permeability characteristics of glomeruli in vitro. The purpose of this study was to determine if the increased glomerular levels of cAMP were related to the protective effects of CsA on an increase in Palbumin by FSGS sera. Glomeruli from Sprague-Dawley rats following intraperitoneal administration of CsA (25 mg/kg/day), cremophore (25 mg/kg/day), or saline for 5 days were incubated with 1:50 dilution of serum from three FSGS patients or with pooled normal human serum prior to calculation of Palbumin. Glomerular cAMP was measured by radioimmunoassay. Glomerular ultrastructural changes were assessed by transmission electron microscopy (TEM). Serum from three FSGS patients markedly increased Palbumin of glomeruli from saline or cremophore treated rats (saline, 0.68+/-0.08; 0.72+/-0.07; 0.70+/-0.07; and cremophore, 0.79+/-0.05; 0.81+/-0.02; 0.79+/-0.01; n=25 glomeruli in each group). In contrast Palbumin of glomeruli from CsA treated rats was not increased by any of the three FSGS sera tested (0.03+/-0.02; 0.04+/-0.05; 0.02+/-0.07, n=25 glomeruli in each group). Glomerular cAMP (pmol/mg of protein) increased 5 fold in CsA treated rats (328+/-26; 5 rats) compared with cremophore or saline treated rats (87+/-24 and 65+/-23, P<0.01; 5 rats in each group). The glomerular basement membrane appeared to be thickened and the lamina densa had an irregular appearance after treatment with CsA. No ultrastructural changes of glomerular epithelial or endothelial cells were evident. We conclude that CsA may have a direct protective effect on the glomerular filtration barrier in FSGS. We postulate that increased levels of glomerular cAMP by CsA may play an important role in protecting the glomerular Palbumin effect of the FSGS factor and may contribute to remission of proteinuria in FSGS patients.     

Pardaxin, a new pharmacological tool to stimulate the arachidonic acid cascade in PC12 cells

BACKGROUND: Calcium channel blockers (CCBs) are known to have differential effects on both changes in proteinuria as well as progression of diabetic nephropathy. No clinical study, however, has evaluated whether the differential antiproteinuric effects of CCBs may be explained by their effect on glomerular membrane permeability. We, therefore, tested the hypothesis that certain subclasses of CCBs reduce proteinuria by changing size selectivity of the glomerular membrane, hence changing its permeability. METHODS: Twenty-one patients with type 2 diabetes and the presence of nephropathy with hypertension were randomized to receive either diltiazem CD or nifedipine GITS after baseline data for mean systolic and diastolic pressure, urinary protein excretion, glomerular filtration rate, renal plasma flow, neutral dextran and IgG clearances were obtained. Glomerular filtration rate, renal plasma flow, neutral dextran and IgG clearance were measured every three months, arterial pressure and heart rate every month. Patients were followed for 21 months. RESULTS: At 21 months, both patient groups had similar levels of blood pressure control, however, only the diltiazem group had a change in proteinuria (4+/-10%delta, nifedipine vs. -57+/-18%delta, diltiazem; P < 0.001) with improvement in glomerular size selectivity and change in IgG clearance. CONCLUSIONS: These data support the hypothesis that CCBs that provide sustained reductions in proteinuria do so, in part, by improving glomerular size permselectivity.     

Effect of isovolaemic haemodilution on visual outcome in branch retinal vein occlusion

The relationship between the activation of platelets (PLT) in urine and renal histological findings in children with IgA nephropathy (IgAN), thin basement membrane disease (TBMD), and minimal-change nephrotic syndrome (MCNS) was examined. The ratio of activated PLT to total PLT (activated and nonactivated PLT) was examined by double immunofluorescence using rhodamine-conjugated P selectin antibody (activated PLT) and fluorescein isothiocyanate conjugated PLT membrane glycoprotein antibody (GPIIb/IIIa, total PLT); the effect of urine on activation on PLT was also investigated. The number of activated PLT and the ratio of activated PLT to total PLT in urinary sediments were significantly higher in children with IgAN with diffuse mesangial proliferation than in those with TBMD or MCNS. PLT were activated by addition of urine in 13 out of 27 children with IgAN, and the activity was higher in the urine of those with active glomerular or interstitial lesions, while the urine of children with TBMD or MCNS had no effect. The presence of activated PLT and the effect of urine on PLT activation may be associated with the active glomerular or interstitial lesions in IgAN.     

The effect of angiotensin-converting enzyme inhibitors on proteinuria in chronic glomerulonephritis

The effect of two angiotensin-converting enzyme (ACE) inhibitors, lisinopril and captopril, on proteinuria and renal haemodynamics was investigated in 11 hypertensives (9 men, 2 women; mean age 46 +/- 16 years) with proteinuria (> 1.5 g/24 h) due to chronic glomerulonephritis and impaired renal function (glomerular filtration rate < 75 ml/min). In a randomized and double-blind cross-over trial the patients received, each time for six weeks, either lisinopril (5 mg/d, sometimes increased to 10 mg/d after 3 weeks) or captopril (twice daily 12.5 mg, sometimes increased to twice 25 mg after 3 weeks). Initially and between the individual treatment phases they were on a placebo phase for 4 weeks. The following were measured: protein excretion, including fractional clearance of albumin and IgG, plasma-renin activity and renal haemodynamics. Protein excretion was not significantly reduced by either drug (placebo: 7.1 +/- 4.0 g/d; lisinopril: 5.1 +/- 2.8 g/d; captopril: 5.4 +/- 3.0 g/d). Albumin excretion and fractional albumin clearance were significantly decreased only by lisinopril (P < 0.05), not by captopril. Plasma-renin activity was increased more by lisinopril than captopril (Placebo: 1.0 +/- 0.9 ng/ml.h; lisinopril: 5.2 +/- 2.8 ng/ml.h [P < 0.05]; captopril: 1.8 +/- 1.3 ng/ml.h [P < 0.05]). The renal haemodynamics was only slightly influenced by either drug, but captopril significantly decreased the filtration fraction in the presence of chronic glomerulonephritis and renal failure. - Resulting from their influence on the renin-angiotensin-aldosterone system, ACE inhibitors have, in addition to their known action on renal haemodynamics, an independent effect on the loading barrier of the basal membrane of the kidney.     

Interleukin-12 and interferon-gamma production in childhood idiopathic nephrotic syndrome

Cellular immune disturbances, and T lymphocyte function in particular, have been previously implicated in idiopathic nephrotic syndrome (INS) of childhood. There are different patterns of cytokine expression in various forms of glomerulonephritis, which suggests that local production of these peptides plays an important role in the pathogenesis and progression of glomerulonephritis. To investigate T-cell and monocyte/macrophage cytokine production in INS, interleukin-12 (IL-12) and interferon-gamma (IFN-gamma) production by peripheral blood mononuclear cells (PBMC) of 11 children with steroid-sensitive nephrotic syndrome (SSNS), 9 with focal segmental glomerulosclerosis (FSGS), and 17 healthy controls was determined. Children with SSNS were studied in relapse, during corticosteroid treatment, and in stable remission, off corticosteroid treatment. IL-12 was not detected in serum, urine, and in supernatants of unstimulated PBMC. IL-12 production by concanavalin A (Con A)-stimulated PBMC of children with SSNS and FSGS was not different from controls. IFN-gamma production by Con A-stimulated PBMC was decreased in children with relapsing SSNS, both in relapse and and during corticosteroid treatment. However, in stable remission it was similar to controls. Markedly decreased IFN-gamma production (P<0.001) was observed by pokeweed mitogen-stimulated PBMC of relapsing SSNS patients and moderately decreased production by PBMC of FSGS patients. This study has established a decreased production of IFN-gamma by PBMC of relapsing SSNS and FSGS patients, but does not allow differentiation between these two different conditions. IL-12 did not have a pathogenic role in either SSNS or FSGS.     

The supinator notch sign in rheumatoid arthritis

Unconcentrated CSF and 200 times diluted serum samples from 192 patients were examined by agar electrophoresis; their albumin and transferrin content were determined simultaneously by radial immunodiffusion. Using the data on transferrin and albumin concentrations in serum and cerebrospinal fluid, the transferrin/albumin index was calculated in a similar way to the IgG/albumin index. Normally the transferrin/albumin index is 1.68 (n = 77; S.D. = 0.22). If the permeability of the blood-CSF barrier increases, the transferrin/albumin index gradually decreases to 1. If the tau-globulin fraction is increased on the agar pherogram, the transferrin/albumin index will be greater than 2.34 (mean + 3 S.D.).     

A serological survey of measles vaccine in a rural region of Eski?ehir in Turkey

Haematuria and proteinuria are important symptoms of primary and secondary nephropathies. We report three african children presenting to our center in whom infection with S. haematobium resulted in haematuria and proteinuria. The third patient concomitantly suffered from steroid-sensitive relapsing nephrotic syndrome with the histological features of focal and segmental glomerulo-sclerosis. The diagnosis was in all cases established by light microscopy and urinary symptoms improved after treatment with praziquantel. In the third patients long term remission of the nephrotic syndrome could be maintained after 4 doses of praziquantel for recurrent bladder symptoms. We conclude that bilharziosis must be considered in the differential diagnosis of children with haeamturia and proteinuria even in Europe. The diagnosis can be established easily by light microscopy and an effective and low-risk treatment (with Praziquantel) can be offered.     

Low dose angiotensin converting enzyme inhibition and glomerular permselectivity in renal transplant recipients

In this study, we determined the fractional clearance of neutral polydisperse dextrans (theta D) and monodisperse dextran sulfate (theta DS) to describe glomerular size and charge selectivity in 25 renal transplant recipients with proteinuria. Thirteen were treated with low dose lisinopril for six months (group 1) and 12 patients without ACE inhibitor therapy formed group 2. Mean arterial blood pressure was stable (group 1, 112 +/- 4; group 2, 109 +/- 2 mm Hg at baseline and after 6 months) whereas creatinine clearance, glomerular filtration rate and renal plasma flow decreased nonsignificantly but were comparable at any time. Lisinopril treatment lowered filtration fraction (22 +/- 2 vs. 19 +/- 2%, P = 0.07) whereas no change was seen in group 2 (20 +/- 2%). The fractional protein excretion (mg urinary protein per day/ml creatinine clearance per day) was stable in group 1, but significantly increased in group 2. The same pattern was found for theta D larger than 56 A. theta DS was stable and consistently elevated in both groups at any time. We conclude that low dose ACE inhibitor treatment in proteinuric renal transplant recipients stabilizes glomerular size selectivity independently of its systemic hemodynamic effects.     

Factors relating to urinary protein excretion in children with autosomal dominant polycystic kidney disease

Adults with autosomal dominant polycystic kidney disease (ADPKD) who have overt proteinuria (>300 mg/d) have higher mean arterial pressures, lower creatinine clearances, larger renal volumes, and a more aggressive course of renal disease than ADPKD patients without proteinuria. This study examines the relationship between proteinuria and microalbuminuria and similar factors in ADPKD children. A total of 189 children from 81 ADPKD families was included in the analysis. The ADPKD children (n = 103) had significantly greater urine protein excretion rates than the non-ADPKD children (n = 86) (3.9+/-0.3 versus 2.8+/-0.2 mg/m2 per h, P < 0.001). Children with severe renal cystic disease (> 10 cysts; n = 54) had greater protein excretion than those with moderate disease (< or = 10 cysts; n = 49) (4.4+/-0.5 versus 3.3+/-0.2 mg/m2 per h, P < 0.05). The ADPKD children had significantly greater albumin excretion rates than the non-ADPKD children (32+/-6 versus 10+/-2 mg/m2 per 24 h, P < 0.001), and a higher percentage of ADPKD children had significant microalbuminuria (>15 mg/m2 per 24 h in boys and >23 mg/m2 per 24 h in girls) than their unaffected siblings (30% versus 10%, P < 0.05). Thirty percent of ADPKD children had albuminuria and 23% had overt proteinuria. For all ADPKD children, there was no correlation between proteinuria and hypertension. However, there was a significant correlation between urinary protein excretion and diastolic BP among children diagnosed after the first year of life (r = 0.23, P < 0.05). Therefore, proteinuria and albuminuria occur early in the course of ADPKD and may be markers of more severe renal disease.