Francisco Coronel

Endogenous Testosterone, Muscle Strength, and Fat-Free Mass in Men With Chronic Kidney Disease

OBJECTIVE Testosterone deficiency is a common finding in men with chronic kidney disease (CKD). Testosterone is thought to play an important anabolic role in muscle synthesis, and muscle wasting is an important and deleterious characteristic of protein-energy wasting (PEW) in CKD. It is presently unknown if reduced endogenous testosterone associates with features of muscle wasting in men with CKD. METHODS This was a cross-sectional observational study of 267 men with CKD stages 2-4 (mean ± standard deviation age 67 ± 13 years, estimated glomerular filtration rate 42.9 [interquartile range 30.2-56.7] mL/min/1.73 m²) with measurements of endogenous testosterone and surrogates of PEW such as albumin, prealbumin, high-sensitivity C-reactive protein (CRP) and normalized protein nitrogen appearance (nPNA). Fat-free mass was estimated by bioelectrical impedance vector analysis (BIVA) and muscle strength by handgrip dynamometry. RESULTS Across decreasing thirds of testosterone distribution, patients were incrementally older and CRP levels rose significantly. Prealbumin, hemoglobin, nPNA, handgrip strength, and BIVA estimated surrogates of muscle mass and nutritional status (fat-free mass, body cell mass, and phase angle) were progressively reduced (P < .05 for all). In multivariate regression analyses including age, renal function, and other important confounders, testosterone significantly and independently contributed to explain the variances of handgrip strength and fat-free mass (P < .05 for all). CONCLUSIONS Endogenous testosterone independently associates with muscle strength and fat-free mass in men with moderate CKD. It is plausible that the reduction in testosterone levels that accompanies CKD may further contribute to the procatabolic environment leading to muscle wasting.

Captopril, proteinuria and peritoneal protein leakage in diabetic patients.

Francisco Coronel, MD, PhD, Servicio de Nefrologia, Hospital Universitario San Carlos, E-Madrid 28040 (Spain) Dear Sir, Several authors have noted a decrease in proteinuria in patients with diabetic nephropathy receiving captopril [1, 2]. This effect has been ascribed to glomerular hemod-ynamic changes caused by the blocking of angiotensin II efferent arteriole receptors, together with improved blood pressure control. However, it is possible that an-giotensin-converting enzyme blockers could improve proteinuria through other mechanisms, such as modification of vessel wall permeability. Diabetic patients included in our continuous ambulatory peritoneal dialysis program during the first months of dialysis showed an important peritoneal protein loss which declined progressively with time when stabilization of blood glucose [3] and/or blood pressure was obtained, as it occurs in diabetic nephropathy where proteinuria is lowered by strict metabolic control [4]. These patients offer an in vivo experimental model for the study of protein leakage in two different vascular systems: (1) the capillaries of the glomerular tuft, influenced by changes in hydrostatic pressure secondary to blood pressure per se and by the action of angiotensin II on efferent arterioles and (2) peritoneal cavity vessels, representatives of normal capillaries without efferent arterioles, and thereby affected principally by blood pressure. We studied proteinuria in 12 diabetic patients who received captopril for a 4-week period before starting on continuous ambulatory peritoneal dialysis. In 9 of these patients, upon starting peritoneal dialysis, captopril therapy was interrupted for a 4-week period, after which it was reintroduced for a similar period. The patients received no other antihypertensive agent during the period of study. Mean doses of captopril were 50 mg/day. Peritoneal protein leakage was evaluated both with and without associated captopril therapy. Both proteinuria and peritoneal protein leakage were reduced with the low doses of captopril. Proteinuria was lowered from 4.54 ± 2.9 g/day precaptropil to 2.9 ± 1.59 g/day with captopril (p < 0.01) without changes in serum creatinine or blood pressure. Peritoneal protein leakage decreased from 7.6 ± 3.0 g/day precaptopril to 4.0 ± 1.7 g/day with captopril (p < 0.05) with a small decrement in mean blood pressure. Two patients included in the study whose blood pressure actually increased also showed reduced protein losses. These data support the hypothesis that captopril could be exerting a proteinuria-reducing effect through additional mechanisms and not only by lowering blood pressure and acting on agiotensin

Early initiation of peritoneal dialysis in diabetic patients

Objective. Starting dialysis earlier in diabetic patients than in other patients with chronic kidney disease slows the progression of some diabetic complications, and could affect the survival outcome. The aim of this study is to assess the effect of starting dialysis early in diabetic patients on survival and hospitalization outcome. Material and methods. One-hundred diabetic patients on peritoneal dialysis (PD), 54 with type 1 and 46 with type 2 diabetes, were reviewed. Renal function was estimated by Modification of Diet in Renal Disease-7 (MDRD-7). The patients comprised two groups according to average MDRD-7 (7.7 ml/min/1.73 m2): group I > 7.7 (56 patients) and group II ≤ 7.7 (44 patients). Survival was analysed by Kaplan–Meier plots and Cox hazard regression for the different variables. Results. MDRD-7 values (mean±SD) at the start of PD were 10.6±2.1 in group I and 5.4±1.2 in group II (p<0.001). Serum albumin (p<0.001) and haematocrit values (p=0.013) were higher in group I, while glycosylated haemoglobin was higher in group II. Kaplan–Meier plots showed higher survival, at 3 years, in group I than in group II (61% vs 39%, p=0.007). In patients with type 2 diabetes there was also greater survival in patients who began PD early compared with later PD initiation. In univariate analysis cerebrovascular pathology had a major influence on survival (odds ratio 2.94, 95% confidence interval 1.3–6.3, p=0.006). Multivariate analysis showed that age and initial serum albumin, and comorbidities such as cerebrovascular disease and cardiac failure, were the factors with the greatest impact on survival. Conclusions. Early initiation of peritoneal dialysis in diabetic patients seems to improve patient survival. Initial serum albumin and age, and the presence of cerebrovascular pathology and cardiac failure are critical factors affecting survival outcome.

Efficiency of three different hemodialysis membranes for plasma porphyrin removal

To assess the capability of three different membranes to remove porphyrins, plasma and dialysate porphyrin levels were fluorometrically measured in 10 patients with end-stage renal failure who were on hemodialysis. Three different hemodialysis membranes were used: cuprophan, polyacrylonitrile, and cellulose triacetate. Total plasma porphyrin concentrations decreased after dialysis, but to a lesser extent when using the cuprophan membrane (19%) than with the polyacrylonitrile (26%) or cellulose triacetate (30%) membranes (P < 0.01). However, since the free plasma porphyrin fraction remained unchanged, it can be assumed that the equilibrium between protein-bound and non-protein-bound (free) porphyrins is displaced toward the latter fraction. Dialysate porphyrin levels were lower (P < 0.01) when using the cuprophan membrane (10.1 micrograms/session) than when using polyacrylonitrile (17.8 micrograms/session) and cellulose triacetate (21.9 micrograms/session). Although most of the plasma porphyrins are protein bound, our results show that hemodialysis can remove significant amounts of non-protein-bound (free) porphyrins. The polyacrylonitrile and cellulose triacetate membranes had a greater capacity for porphyrin removal than cuprophan. Thus, two high-permeability membranes (polyacrylonitrile and cellulose triacetate) should be used whenever a reduction of plasma porphyrin levels is desired.

Changes in peritoneal membrane permeability and proteinuria in patients on peritoneal dialysis after treatment with paricalcitol − a preliminary study.

BACKGROUND Patients on peritoneal dialysis (PD) have protein loss through peritoneal membrane (PM) and experience changes in permeability of the membrane. Paricalcitol is a selective vitamin D receptor activator with an effect upon systemic inflammation and an inhibitory effect upon the renin-angiotensin-aldosterone system (RAAS). METHODS This study explores the possible effect of paricalcitol upon the PM in 23 patients on PD with high iPTH levels. Peritoneal kinetic studies were performed before and after paricalcitol, measuring also ultrafiltration/ day, peritoneal protein losses and proteinuria. Results were compared with a control group of 15 patients not receiving any form of vitamin D. RESULTS With a mean dose of 1.3 μg/day, peritoneal protein loss decreased from 0.91 ± 0.35 to 0.76 ± 0.26 g/l (15.4%) (p = 0.007) and from 7.55 to 6.46 g/d (p < 0.033), and ultrafiltration increased from 844 to 1,002 ml/d (15.8%) (p = 0.037) and from 284 to 323 ml/4 h. (NS), with minimal change in the creatinine dialysate/plasma ratio 0.67 ± 0.12 vs. 0.65 ± 0.11. Proteinuria decreased from 1.65 to 1.25 g/l (21.9%) (p = 0.01) and iPTH decreased from 668 ± 303 to 291 ± 148 pg/ml (p < 0.001). In the control group, no changes in peritoneal membrane permeability and proteinuria were found. CONCLUSIONS The results of the study indicate that paricalcitol is effective in treating hyperparathyroidism in patients on PD, and suggest an effect upon proteinuria and PM permeability (not previously reported), with diminished peritoneal protein loss and increased ultrafiltration. The antiinflammatory, antifibrotic and RAAS-modulating actions described for paricalcitol may be responsible for these findings, and could be important for preserving the peritoneum as a dialyzing membrane.

Oral paricalcitol as antiproteinuric agent in chronic kidney disease

BACKGROUND Vitamin D has an important regulatory effect on the renin-angiotensin-aldosterone system, playing a central role in the regulation of proteinuria. We therefore studied the antiproteinuric effect of paricalcitol. METHODS 36 patients with an estimated GFR of 30-90 mL/min/1.73 m² and proteinuria >400 mg/d with a stable dose of ACE inhibitor or ARB for at least 3 months were recruited. Patients received oral paricalcitol 1 µg/day for 12 months. Primary endpoint was decrease in proteinuria from baseline. Secondary endpoints were changes in creatinine, eGFR, serum levels of calcium, phosphorus, iPTH, 25(OH)vitD, C-Reactive Protein and blood presure. RESULTS Mean proteinuria was 2806 mg/d and fell to 2199 mg/d at month 6 (p<.0001) and 1931.5 mg/d at month 12 (P<.0001). Patients with >3000 mg/d baseline proteinuria (n=12) saw smaller relative reductions in proteinuria (5956.9±2492.6 mg/d to 4220.4±2613 mg/d at 12 months) than patients with <3000 mg/d baseline proteinuria (1371±627.5 mg/d to 821.3±491.5mg/d at 12 months). There were no changes in BP, eGFR and CRP. We observed significant changes in serum levels of calcium, phosphorus, iPTH, 25(OH) vitamin D. CONCLUSION Our study shows an important reduction in proteinuria with a low dose of oral paricalcitol in CKD, that is particularly robust with baseline proteinuria between 1-3 g/d.

Abdominal Wall Leakage on CAPD: Usefulness of Ultrasonography

Dr. Francisco Coronel, Servicio de Nefrología, Hospital Universitario San Carlos, Plaza de Cristo Rey s/n, E-28040 Madrid (Spain) Dear Sir, Extraperitoneal leakage of dialysate fluid is a common problem in patients undergoing CAPD [1]. Previous studies report the usefulness of CT peritoneography [1, 2] in the diagnosis of these problems. We present here a case to demonstrate the risk of complications due to peritoneography and the role of ultra-sonographic techniques. A 69-year-old woman with end-stage renal disease due to interstitial damage was put on CAPD in October 1990. In July 1992, the catheter was removed after exit site infection resistant to antibiotic treatment. Six months latter, a Staphylococcus aureus peritonitis was treated with an uncomplicated course. One month later, dialysis balance was progressively decreasing, with acceptable biochemical values. Body weight increased, and an abdominal wall edema appeared, no per-icatheter leakage could be demonstrated. Ultrasonography was performed to detect the leakage. Ultrasonography showed abdominal wall fluid collection (near the site of catheter insertion) probably due to peritoneal leakage (fig. la). With this finding, a CT scan was performed with 50 ml of nonionic contrast media (Omnitrast-Schering) infused together with one liter of dialysate through the peritoneal catheter; contrast media was observed to pass into the anterior abdominal wall around the albus lineae, entering a big abdominal hernia (fig. lb). Once the leakage had been demonstrated, surgical correction was decided, and the patient was included temporarily in the hemo-dialysis program. Forty eight hours after peritoneography, the patient was admitted into hospital with fever and abdominal pain. Peritonitis was established. Peritoneal drainage Fig. 1. a Abdominal wall ultrasonography (longitudinal image): abdominal wall fluid collection near the site of catheter insertion, probably due to peritoneal leakage, b CT peritoneography: After contrast injection through the peritoneal catheter, contrast could be observed in the anterior abdominal wall around the albus lineae.

A 2 year evaluation of diabetic patients on continuous ambulatory peritoneal dialysis

Nineteen diabetic patients with end-stage renal disease on CAPD were evaluated over a 2 year period. All but one patient was insulin-dependent, with a mean age of 47.7 years. Average time on CAPD was 16.1 months (range, 2-28 months). Thirteen patients were followed for more than 12 months, and nine for more than 18 months. The mean training period was 22.9 days. Good blood glucose control was obtained with intraperitoneal (IP) insulin in all of the patients. Mean blood glucose levels of 125 +/- 23.08 mg/dl were achieved with 103 +/- 38.5 U/day of regular IP insulin. Glycosalated hemoglobin decreased from a mean of 12.7 +/- 2.35% before CAPD to 10.08 +/- 0.97% during CAPD. Peritoneal creatinine clearance remained stable during the study period, with a concommitant decrease (P less than 0.001) in the mean residual renal creatinine clearance. The incidence of peritonitis was one episode per 7.8 patient-months. Average length of hospitalization was 33.24 days/year. Visual acuity remained stable after 1 year in 73% of the 26 eyes evaluated. No amputations were required in more than 2 years of follow-up. Actuarial survival was 100% at 1 year and 86% at 2 years, and the technique survival of CAPD was 91 and 79%, respectively. These results demonstrate that CAPD is a good dialysis procedure for treating diabetic patients with chronic renal failure, and it offers the advantage of controlling glycemia better than other dialysis methods.