The racial prevalence of glomerular lesions in nephrotic adults.

We retrospectively evaluated the prevalence of primary glomerular lesions in adults who had a renal biopsy for nephrotic proteinuria. From July 1975 to May 1994, 340 patients undergoing renal biopsies evaluated at Rush-Presbyterian-St Lukes Medical Center had the primary glomerular lesions of minimal-change disease, focal segmental glomerular sclerosis (FSGS), membranous glomerulonephritis (MGN), membranoproliferative glomerulonephropathy, immunoglobulin A nephropathy, and immunotactoid glomerulopathy. The patients had a mean age of 43 +/- 17 years, 57% were male, and 50% were white, 36% were black, 7% were of other race, and 7% were of unknown race. The distribution of lesions for black patients was minimal-change disease 14%, FSGS 57%, MGN 24%, membranoproliferative glomerulonephritis 2%, immunoglobulin A 2%, and immunotactoid glomerulopathy 1%; for white patients, the distribution of lesions was minimal-change disease 20%, FSGS 23%, MGN 36%, membranoproliferative glomerulonephropathy 6%, immunoglobulin A 8%, and immunotactoid glomerulopathy 6%. The prevalence of FSGS was significantly greater (P < 0.0001) and that for MGN, immunoglobulin A, and immunotactoid glomerulopathy was significantly less (P < 0.05) for black patients compared with white patients. In a logistic regression analysis, race remained the only significant predictor of FSGS (P = 0.0001), with black patients four times as likely to have FSGS as white patients. The distribution of lesions among white patients was similar based on gender, age, and biopsy period. For black patients the distribution was also similar based on gender and age, but over 20 years the incidence of FSGS increased from 39% (1975 to 1984) to 64% (1985 to 1994) (P < 0.01). Thus, significant racial differences in the distribution of primary glomerular lesions exists. This has important prognostic and therapeutic implications for nephrotic adults.

Primary focal segmental glomerular sclerosis in adults: prognostic value of histologic variants.

Primary focal segmental glomerular sclerosis (FSGS) is a clinicopathologic syndrome in which variable amounts of proteinuria are associated with the renal biopsy finding of segmental glomerular scarring in some, but not all, of the glomeruli. Additional histologic features have been described in FSGS, including the position of the scar relative to the vascular and tubular pole of the glomerulus, foam cells, hyalinosis, mesangial deposits of immunoglobulin M, diffuse mesangial hypercellularity, glomerular visceral epithelial cell hyperplasia and hypertrophy, and the extent of associated interstitial fibrosis and tubular atrophy. We performed a retrospective study on 81 patients with biopsy-proven, primary FSGS to determine whether any of the histologic features of FSGS correlated with renal function at the time of biopsy and the incidence of end-stage renal disease at follow-up. Sixty patients were nephrotic and 21 had nonnephrotic proteinuria. Only the degree of interstitial fibrosis correlated with the initial serum creatinine (r = 0.536) and none of the histologic features predicted the presence of nephrotic-range proteinuria at the time of biopsy. Segmental scars involved 21% +/- 14% of the glomeruli per biopsy specimen, but their position within the glomerulus was uniform in only 13% of the cases. Diffuse mesangial hypercellularity was present in 17% of the biopsy specimens, and glomerular epithelial cell lesions were present in 57% of the biopsy specimens. Multivariate analysis showed that only the degree of interstitial fibrosis predicted end-stage renal disease in all 81 patients and in the 60 patients with nephrotic-range proteinuria. The current data do not support different therapeutic approaches in primary FSGS based on histologic subtypes.

Why the double-bag system still remains the best technique for peritoneal fluid exchange in continuous ambulatory peritoneal dialysis.

Since March 1979 (the Italian-French-Spanish meeting in Turin), we have been using the double-bag system for peritoneal fluid exchange in patients on continuous ambulatory peritoneal dialysis (CAPD). This technique, subsequently followed by many others because of the advantages to the patients, still represents the best tool in bag-exchange procedure, because it satisfies the following characteristics: single luer-lock connection; flush-before-fill; simple, safe, and aseptic manipulation; short training period; no carrying bag; good patient acceptance; and low incidence of exogenous peritonitis. In 13 years with 237 patients selected for double-bag treatment, we have observed an incidence of 1 episode of peritonitis every 26.6 patient-months. Few clinical CAPD-related complications like hypotension and alterations of Ca-P metabolism were observed, probably as a result of more personalized peritoneal fluid with high Na+ (136 mEq/L) and Ca2+ (3.5 mEqL) concentrations. In the meantime, we have also had available plasticizer-free bags, which eliminated one of the main risk factors in peritoneal sclerosis. The utilization of the plasticizer-free double-bag system, currently adopted by numerous other centers, still remains the best option from a clinical and psychological viewpoint of the patients on CAPD.

Effect of hypertriglyceridemia correction by omega-3 fatty acids on peritoneal transport in continuous ambulatory peritoneal dialysis patients.

Lipid abnormalities, both hypercholesterolemia and particularly hypertriglyceridemia (hyperTg), are common in long-term continuous ambulatory peritoneal dialysis (CAPD) patients. Hyperviscosity and rheological alterations have been proposed as major hemodynamic problems in hyperTg patients. The aim of this study was to evaluate whether a hyperTg correction by employing omega-3 fatty acids (omega-3) affects peritoneal transport. Six hyperTg (> 700 mg/dL) CAPD patients were treated with 2-3 g/day of omega-3 until normal Tg values were achieved. The assessment of peritoneal dialysis efficacy was performed by evaluating the peritoneal equilibration test (PET) before omega-3 supplementation, when normal Tg levels were reached, and 3 weeks after stopping therapy when hyperTg returned. When normal Tg levels were reached, a small but significant improvement of urea and creatinine D/P was noted: 0.85 +/- 0.05 versus 0.93 +/- 0.03 (p < 0.05) and 0.78 +/- 0.03 versus 0.86 +/- 0.05 (p < 0.05), respectively, with negative correlation between D/P of urea and Tg. These preliminary data demonstrate that a hyperTg correction with omega-3 may induce an increase in peritoneal transport of small molecules in CAPD.

Peritoneal sclerosis: role of plasticizers in stimulating interleukin-1 production.

The role of plasticizers (PLS) in inducing water flow inhibition and peritoneal sclerosis has been demonstrated in both in vivo and in vitro studies. Interleukin-1 (IL-1) has been shown to be a regulator of fibroblast proliferation as well as collagenase production. The aim of this study was to evaluate the role of PLS in stimulating mononuclear cell IL-1 secretion. Two cultures containing 10(3) cells/mL were obtained from 14 healthy subjects. One was used as the control, and the other was mixed with diethylhexylphthalate (DEHP) to reach a final concentration of 2.8 x 10(-3) M. After 4 hours the samples were centrifuged, and the supernatants were tested by radioimmunoassay for IL-1 alpha and IL-1 beta. The results showed a significant increase in both IL-1 alpha and IL-1 beta production in DEHP-stimulated cells in comparison to the controls: 42.6 +/- 15.4 versus 29.3 +/- 10 ng/L (p < 0.015) for IL-1 alpha, and 153.6 +/- 55 versus 113.6 +/- 32 ng/L (p < 0.03) for IL-1 beta In conclusion, PLS added to mononuclear cells were able to induce IL-1 secretion. This mechanism could be responsible, at least in part, for the development of peritoneal sclerosis. Thus the employment of plasticizer-free bags should be elective in peritoneal dialysis.

Combined hemodialysis-hemoperfusion in the treatment of secondary hyperparathyroidism of uremic patients.

Hyperparathyroidism and its related symptoms such as bone pain, soft-tissue calcifications and pruritus often get worse during dialysis treatment. We have treated 12 cases among 170 patients on regular dialysis by using coated charcoal (150 g/cartridge) in combination with standard hemodialysis. During a 6-month treatment period, without changing medical therapy and diet regime, the patients reported a marked relief from pruritus. Parathyroid hormone (PTH) levels changed from 552 +/- 86 to 364 +/- 62 pg/ml (p less than 0.001) compared to the pretreatment period, Plasma PO4(3-) changed in the same period from 6.9 +/- 1.8 to 4.6 +/- 1.5 mg/dl (p less than 0.005). The results obtained indicate a relationship between PTH, serum plasma PO4(3-) levels and pruritus. The mechanism which may be involved is that hemoperfusion removes PTH excess by absorption. Our treatment reducing PTH levels resulted in a marked relief from pruritus and other symptoms, suggesting that patients in this condition, before undergoing surgical parathyroidectomy, may be usefully treated with this therapeutic modality.

Spontaneous ascites filtration and reinfusion (SAFR) in cirrhotic patients.

Since knowledge about the pathogenesis of hepato-renal syndrome (HRS) is incomplete, the therapy is empiric and supportive. While a number of specific therapeutic measures have been attempted, none has been proved to be of practical value. We describe a very simple technique for concentration of ascitic fluid obtained with spontaneous filtration by gravity. We have been treating with this new device 4 patients affected by HRS with ascites refractory to diuretics. We obtained a rapid disappearance of ascites and improvement in clinical condition. The simplicity and the ease of operation make this technique feasible for repeated chronic ambulatory treatment.