P. Cappelli

Lipids in the Progression of Chronic Renal Failure

Lipid disturbances have been linked to the progression of chronic renal disease. We examined 52 patients with a creatinine clearance (CCr) of 38.5 +/- 7.9 ml/min due to various nephropathies, on free diet. Bimonthly, over a 12-month period, we assessed: serum creatinine (Cr); CCr; daily urinary urea excretion; urinary protein excretion per unit of residual renal function (UProt/CCr); total, HDL, VLDL and LDL cholesterol; triglycerides; Apo A, Apo B. Chronic renal failure was progressive in 22 patients with a slope of 1/Cr-0.00358 +/- 0.00247, stable in 30 with a slope of 0.00420 +/- 0.00285. Lipid parameters did not differ significantly between the two groups but for the lower Apo A and Apo A/Apo B ratio values in the progressive group. Overall slope inversely correlated with basal CCr; in the progressive patients the slope correlated with the percentage variation of UProt/CCr and only partially with the altered Apo profile.

Leukocyte adhesion molecules and leukocyte-platelet interactions during hemodialysis: effects of different synthetic membranes.

Membranes made from synthetic polymers, in general, are considered as being biocompatible membranes and tend to be treated as a homogeneous group. However, all of these membranes have multiple and different characteristics that may contribute to interactions with blood components. As a consequence, the biocompatibility profile of synthetic membranes may vary. In the present cross-over study, we examined by flow cytometry the effects (expressed as % change from predialysis values) of three different synthetic polymers (polysulfone, PSF; polyacrylonitrile-co-sodium methallyl sulfonate, AN69; ethylenevinylalcohol, EVAL) on the expression of leukocyte adhesion molecules (CD11b/CD18, CD15s) and the interactions between leukocytes and platelets under conditions of routine clinical use. For neutrophils, a statistically significant difference was found in CD15s expression for EVAL as compared to AN69 (p<0.05) and in CD11b/CD18 expression for PSF as compared to both EVAL (p<0.01) and AN69 (p<0.05). No difference between membranes was found on the expression of such adhesive molecules on monocytes. Significant differences in platelet-neutrophil (but not in platelet-monocyte) coaggregate formation were observed between PSF and both EVAL (p<0.001) and AN69 (p<0.01). Reactive oxygen species production by neutrophil population during hemodialysis was significantly different between each pair of synthetic polymers (PSF vs EVAL, p<0.001; PSF vs AN69, p<0.001; AN69 vs EVAL, p<0.05). Our data demonstrate that in terms of leukocyte adhesion receptors and platelet-leukocyte interactions, the biocompatibility profile of the synthetic membranes polysulphone, AN69 and EVAL shows many similarities but also several significant differences. Our results support the concept that biocompatibility evaluation of each membrane should be based exclusively on data generated by that membrane in order to avoid errors based on assumptions about group characteristics.

Low-Dosage Ibopamine Treatment in Progressive Renal Failure: A Long-Term Multicentre Trial

A multicentre trial (11 nephrology centres) was carried out to test the effects of ibopamine, an orally active dopamine-like drug, on the progression of chronic renal failure. For a 2-year period 189 chronic renal failure patients (serum creatinine level 1.5-4.0 mg/dl) were observed. They were homogeneous for basic nephropathy, degree of residual renal function, blood pressure, and proteinuria. The patients were randomly divided into two groups: 96 took ibopamine at a dosage of 100 mg/day (group A) and 93 served as controls (group B). All were on a low-protein diet (mean 0.8 g/kg body weight). By the end of the observation period, the rate of decrease of the renal function indexes in time proved significantly slower (1.8 times) in group A than in group B. The survival curves for renal function (pre-established end points were creatinine level increases equal to or > 20% and equal to or > 40% of the basal values) proved significantly better (p < 0.02 and p < 0.002 respectively) in group A than in group B. The mean plasma creatinine values rose by 17% in group A and by 36% in group B. The creatinine clearance decreased by 5% in treated patients and by 14% in the controls. Statistical analysis ruled out any possible centre effect. The trial suggests that low-dosage ibopamine administration may be used as a valid and safe pharmacological adjunct for retarding the progression of renal failure in patients with mild or moderate chronic renal impairment.

Neurological and Psychiatric Disorders in Renal Diseases

Neurological abnormalities specifically related to uremia constantly occur in patients with end-stage renal disease (ESRD), although they only become clinically well defined in severe acute renal failure (ARF) or late in the course of chronic renal failure (CRF) and sometimes in connection with metabolic acidosis and/or electrolyte disturbances secondary to renal disease (1–5).

Neurological Complications of the Uremic Syndrome

Neurological abnormalities specifically related to uremia occur constantly in chronic renal failure (CRF), although they do not become clinically well defined until late in the course of the uremic syndrome. These abnormalities can affect the central (encephalopathy) or peripheral (polyneuropathy) nervous system or both.

Effects of Nutritional Treatment on the Course of Uremic Neuropathy

Clinical and electrophysiological findings show that, in spite of conventional conservative and regular dialysis treatment, uremic neuropathy persists and progresses [1] until after kidney transplant normality has been reached. However, papers referring to this topic do not generally give details of the diet, which is vaguely referred as a low-protein diet. No conclusions can thus be drawn on the real role of such a treatment on the progression of uremic neuropathy.

Nonsteroidal Anti-Inflammatory Drugs as Risk Factor for Renal Failure from Acute Uric Acid Nephropathy

Prof. Alberto Albertazzi, Institute of Nephrology, University of Chieti, S. Camillo De Lellis Hospital, Via C. Forlanini, I-66100 Chieti (Italy) Dear Sir, The risk for a rapidly occurring form of renal insufficiency due to acute uric acid nephropathy exists in patients affected by lymphoor myeloproliferative disorders as a result of rapid cell turnover, often during chemotherapy [1]. Our clinical experience shows, however, that the same pattern may appear in subjects who show no signs of neoplastic pathology and have no positive history of hyperuricemia or gout. From January 1980 to November 1985 we observed 9 patients, all males between 20 and 46 years of age, with acute renal failure due to intratubular obstruction by uric acid crystals. They had been apparently healthy until the acute episode and had no preceding history of renal disease; only 2 cases suffered from episodic emission of gravel without hyperuricemia. The clinical symptoms consisted of lumbar pain and oliguria. Renal function, on admission, was reduced, in 4 cases by only 60% and returned to normal over 3 days, in the other 5 cases by 90– 95% and more lasting; however, no dialytic treatment was necessary in view of the transitory nature of the oliguria. The diagnosis of acute nephropathy due to uric acide was based on the exclusion of other possible causes and on the report of uric acid/creatinine ratio > 0.9 in random urine samples [2]. In the 5 more serious cases we carried out a renal biopsy which showed the presence of intratubular deposits of uric acid and focal tubular necrosis, mainly in the distal tract. In all the patients, on return of normal renal function, we observed uricuria at the upper limits of the normal range. A few hours before the appearance of acute symptoms, the patients had carried out intense physical activity. The 5 more serious cases had taken nonsteroidal anti-inflammatory drugs as symptomatic treatment for acute lumbago. Intense physical activity, by stimulating an increase in the production of uric acid and a relative dehydration, may predispose to intratubular precipitation of uric acid in subjects who eliminate large quantities of it under normal conditions. Simultaneous treatment with nonsteroidal antiinflammatory drugs aggravates the clinical picture, probably by inhibiting the synthesis of prosta-glandins which antagonize the action of ADH when diuresis is decreased. References Riselbach, R.E.; Bentzel, C.J.; Cotlov, E.; Frei, E.; Freireich, E.J.: Uric acid excretion and renal function in the acute hyperuricemia of leukemia. Am. J. Med. 37:872–884 (1964).

Protective Effect of Calcium-Channel Blockers on the Cyclosporins (CyA)-Related Nephrotoxicity

Cyclosporine (CyA) represents an entirely different class of immunosuppressive agents (1). Acute and chronic nephrotoxicity directly attributable to CyA has tempered the initial enthusiasm surrounding this drug (1). At present the pathogenesis of CyA nephrotoxicity has not been fully elucidated but so far it has been suggested that can be divided chronologically into three broad components: 1) a functional toxicity, due mainly to afferent renal arteriolar vasocontriction (2); 2) a reversible tubulo-toxicity manifested by giant mitochondria and tubular vacuolization and dilatation (3); 3) an obliterative and irreversible arteriolopathy, eventually leading to interstitial fibrosis and nephron loss. Recently a number of reports have suggested that renal allograft recipients receiving CyA and Calcium-channel antagonists have better graft function, a lower incidence of delayed graft function and fewer rejection episodes than those receiving CyA alone (4). The use of calcium-channel antagonists as nifedipine (NIF) in combination with CyA therapy in renal transplant recipients is attractive, as hypertension is common, and because they may potentiate the inhibition of lymphocyte proliferation induced by CyA, the effects of NIF on overall glomerular and tubular functions has not been investigated in patients with stable graft function. Aim of our paper is to assess the effects of NIF on glomerular and tubular function and CyA levels in patients with stable allograft function at least six months after transplantation.

Serum Branch-Chain Amino and Keto Acids in the Nutritional and Immunological Assessment of Uremics on Conservative and Dialysis Treatment

Defective cell-mediated immunity (CMI) is well documented in patients with chronic renal failure (CRF) due to many factors (1). The aim of our study was to examine the effects of CRF on serum branch-chain amino and keto acids (BCAA-BCKA), visceral proteins and CMI.