Radomir Naumovic

Renal biopsy registry from a single centre in Serbia: 20 years of experience

BACKGROUND There is not enough epidemiologic data of biopsy proven renal diseases. This is the first report of clinicopathologic correlations over a period of 20 years from central Balkan country-Serbia. METHODS A retrospective review of reports of 2 362 native renal biopsies performed on patients at the leading nephrology unit in Serbia from 1987 to 2006 was undertaken. Patients were divided in two groups according to age: younger (<60 years old) and older (>or=60 years old). RESULTS The annual incidence of renal biopsies increased from 3.9 p.m.p./year in 1987 to 12.5 p.m.p/year in 2006. The most common clinical syndrome as an indication for renal biopsy was nephrotic syndrome (NS) (53.6%). Membranous nephropathy was the most frequent cause of NS (21.6%). Primary glomerulonephritis (PGN) accounted for about two thirds of all performed biopsies. Non-IgA mesangioproliferative GN was the most frequent primary GN accounting for almost 25% of all PGN in our whole population, while the prevalence of IgA nephropathy was only 12%. Lupus nephritis was the most frequent secondary glomerulonephritis (75.6%). CONCLUSIONS This report represents epidemiological overview on biopsy proven renal disease coming from one specific Balkan country, which was under economic sanctions for almost half the studied period. We are hoping that this register will be the basis for developing not only a national register but also a register that will encompass all Balkan countries.

Effect of donor age on the outcome of living‐related kidney transplantation

The study compared the results of kidney transplantation from living‐related donors older and younger than 60 years. The 273 kidney graft recipients were divided into group 1 (115 recipients of older grafts) and group 2 (158 recipients of younger grafts). The frequency of acute rejection (AR) episodes was similar in both groups but slow graft function occurred more frequently in group 1. The frequency of chronic renal allograft dysfunction in the first post‐transplant year was significantly higher in group 1 than in group 2. Patient and graft survival was significantly worse in group 1. Risk factors for graft loss were the difference between donor and recipient age and AR. Donor age and graft function were risk factors for patient death. Although kidneys from older donors provide a statistically poorer transplant outcome, they are clinically acceptable, especially when waiting time is prolonged and access to dialysis limited.

Effects of Rapamycin on Active Heymann Nephritis

Background/Aim: The effects of rapamycin (RAPA) were examined in active Heymann nephritis (HN), an experimental model of human membranous nephropathy (MN). Current opinion on the therapy of MN is controversial, and medications used for its treatment have not yielded the expected results. Methods: In a two-part study, we examined the effects of RAPA (1.5 mg/kg/day) during the induction phase of HN and on the evolving disease. In both parts, control groups of immunized rats not treated with RAPA and control groups of unimmunized rats were observed and sacrificed concurrently with the treated groups. Results: During the induction phase no significant changes in proteinuria were observed in the group treated with RAPA, in comparison to those in the untreated group (p < 0.001). During the evolving disease RAPA significantly lowered proteinuria (p < 0.001). The characteristic pathohistologic changes and IgG depositions along the glomerular basement membrane were considerably diminished, and infiltration of CD8+ cells completely prevented. Conclusion: RAPA demonstrated beneficial effects on disease progression, given either in the induction phase or during evolving HN. It would be desirable to investigate the effect of RAPA on patients with MN.

Donor Kidney Glomerular Filtration Rate and Post-Transplant Graft Function

This study aimed to estimate the relationship between the single kidney glomerular filtration rate (SKGFR) of a planned kidney transplant and the subsequent graft function and survival of living related kidney recipients (LKRs). Of 180 LKRs with the graft functioning for more than a year, 70 patients without delayed graft function (DGF) or acute rejection (AR) were selected for the study. According to SKGFR, assessed by 99mTcDTPA, the patients were allocated into Group 1, receiving kidney with SKGFR < 50 mL/min (32 patients), and Group 2, with SKGFR > 50 mL/min (38 patients). The database included donor, recipient and transplant variables. No significant difference was found between the patient and graft survival rate, creatinine clearance (CCr) and the rate of CCr change between the groups. Additional evaluation revealed no significant influence of the ratio of SKGFR and the recipients body weight/size on patient and graft outcome. The analysis of factors of influence on patient and graft survival and function revealed the major influence of nonimmunological factors but not of SKGFR of the transplanted kidney. Our study did not confirm the influence of SKGFR on graft function and survival in the LKRs without DGF and AR but the limited number of patients must not be disregarded.

Cyclosporine versus azathioprine therapy in high-risk idiopathic membranous nephropathy patients: A 3-year prospective study.

There is no consensus regarding the modality of therapy for idiopathic membranous nephropathy (IMN), especially for patients who did not react to treatment with cytotoxic drugs. This study followed prospectively for 3-year IMN patients who did not react to Ponticelli protocol comparing effects of 2-year course of cyclosporine (CsA) with azathioprine (Aza) treatment both with small doses of prednisolone. Twenty-three patients were randomly assigned to receive either cyclosporine at 3mg/kg per day (10 patients) or azathioprine at 1.5 to 2mg/kg (13 patients). Both groups were comparable regarding age, sex and renal function, except for proteinuria, which was significantly greater in CsA group (P=0.003). Similar rate of remission of nephrotic syndrome (NS) have been noted at the end of treatment (80% CsA versus 93% Aza). During last year, follow-up relapses of NS were more frequent in Aza group (5 versus 1). A fall in proteinuria was recorded in both groups during treatment, but it rose significantly in Aza group (1.5g/day versus 3.1g/day, P=0.04) and remained unchanged in CsA group (3.9g/day versus 4.1g/day) after treatment cessation. Renal function deteriorated in Aza group (sCr 120.5 versus 269.8μmol/L; P<0.01) and was stable in CsA group. In conclusion, CsA and steroids may be a very important option in the management of high-risk IMN patients. Long-term treatment is necessary for achievement of full therapeutic effect. Treatment with Aza did not have long-term benefits particularly regarding renal function preservation.

Correlation of kidney size with kidney function and anthropometric parameters in healthy subjects and patients with chronic kidney diseases.

Abstract Background/Aim: Echosonography is a simple, noninvasive method of kidney visualization. The objective of this study was to compare the kidney echosonograpic characteristics with the kidney function and anthropometric characteristics in healthy subjects and patients with the chronic kidney disease (CKD). Methods: The study involved 49 patients (21 men; 46.02 ± 14.27 years) with CKD and the control group of 46 healthy persons (20 males; 45.45 ± 18.48 years). Physical examination, kidney echosonography and laboratory analyses including creatinine clearance (Ccr; 24 h and calculated by Cockroft--Gault (C--G) formula) were done in all persons. Results: There was no significant difference in age and sex between two groups but serum creatinine concentration was significantly higher (218.8 vs. 84.5 μmol/L) and Ccr significantly lower (66.44 vs. 94.20 mL/min, C--G) in patient group. The left kidney was larger in both groups, but the only significant difference was in kidney depth (p < 0.01). There was significant correlation between all measured kidney dimensions, volume, parenchymal thickness and serum creatinine concentration and Ccr (C--G) in patient group. In the controls, there was no significant correlation between the kidney size and function, but there was a significant correlation between the kidney width, depth, volume and patients’ age and anthropometric parameters. On the contrary, all analyzed parameters of kidney size, except volume, did not correlate significantly with the anthropometric parameters of patients. Conclusion: Kidney size of patients with CKD correlated significantly with kidney function, while correlation with anthropometric parameters, which is otherwise present in healthy subjects, was lost in patients with CKD.

Could the Level of Serum Albumin Be a Method for Assessing Malnutrition in Hemodialysis Patients

BACKGROUND Traditionally, serum albumin concentration has been used for assessing the nutrition status of hemodialysis patients despite evidence that the level is also affected by inflammation and many other underlying disorders frequently present in these individuals. The authors evaluated albumin as a nutrition parameter, comparing it with more specific anthropometric parameters. METHODS The study included a cohort of 271 patients. The analysis involved data obtained after patients entered the study (1994-2004). Anthropometric measurements included skinfolds, mid-arm circumference, mid-arm muscle circumference, percentage of body fat, body mass index, body height, and dry weight. Kt/V and normalized protein catabolic rate were also determined and laboratory analyses undertaken. RESULTS Serum albumin was only weakly correlated with mid-arm circumference (r = 0.12), mid-arm muscle circumference (r = 0.15), and fat-free mass (r = 0.12). Common factor analysis of nutrition parameters uncovered latent variables, but serum albumin was not associated strongly with them. The sensitivity of albumin in detecting malnutrition was 24%, with a specificity of 88% and a predictive value of 74%. Graphic analysis showed disagreement in albumin levels with percentage of body fat and mid-arm muscle circumference. CONCLUSION Serum albumin determination was shown to be a test with low sensitivity and specificity for evaluating malnutrition in hemodialysis patients. The values correlated weakly and showed graphic disagreement with anthropometric parameters. Therefore, methods that measure percentage of body fat and muscle mass should be used together or instead of serum albumin level for assessing the nutrition status of hemodialysis patients.

Factors affecting graft function in pediatric and adult recipients of adult live donor kidney transplants.

Abstract:  The aims of this investigation were to compare changes of function of adult living kidney grafts transplanted into adult and child recipients and to analyze factors associated with graft function during the first post‐transplant year. The study involved 53 adult and 23 pediatric recipients with immediate graft function and without complications that could influence graft function. In comparison to children, adult recipients and their donors were older, and having been longer on hemodialysis they had received more transfusions. Although similar baseline graft function – GFR0 was transplanted in both groups, absolute and relative GFR in adults rose and maintained stable, while in children absolute GFR decreased and remained similar to the GFR0 until the end of the study. Significant predictors of kidney function in both adult and child recipients were donor age, ratio between GFR0 and recipient BSA, induction immunosuppression, and systolic hypertension. In conclusion, the function of adult live kidney grafts changed differently in children and adults because of different functional requirements of recipients but donor age, induction immunosuppression and hypertension are significant predictor of graft function in both adults and children.

The importance of MDR1 gene polymorphisms for tacrolimus dosage.

Polymorphisms of the multi drug resistance (MDR1) gene cause variability in P-glycoprotein mediated metabolism of tacrolimus. The aim of this study was to examine the relationship between MDR1 gene single nucleotide polymorphisms (SNPs) and their haplotypes with dosage of tacrolimus in kidney transplant recipients who were cytochrome (CYP) 3A5*3 homozygotes. This study included 91 kidney transplant recipients followed two years after transplantation. Detection and analysis of MDR1 gene polymorphisms in positions C1236T, G2677T/A and C3435T were performed using PCR method. Patients with variant alleles for SNPs G2677T/A and C3435T required higher doses of tacrolimus and had a lower level/dose (L/D) ratio than patients with wild alleles or heterozygotes. That difference was the most obvious for SNP G2677T/A where TT homozygotes required significantly higher doses of tacrolimus during whole follow-up. Their L/D was significantly lower in the first month after transplantation. Recipients with CTT/TTT haplotype also had lower L/D than those with CGC/TTT and CGC/CGC, significantly in the 10th and 20th days after transplantation respectively (p<0.05). Our results demonstrate that TT homozygotes at positions G2677T/A and C3435T required a higher tacrolimus dose than those with wild alleles or heterozygotes. It may be helpful in the prevention of tacrolimus nephrotoxicity early after transplantation.

Inflammatory markers as mortality predictors in continuous ambulatory peritoneal dialysis patients

Abstract Background/Aim: Besides peritonitis, the most common complication, indicators of chronic inflammation are also present in patients treated by peritoneal dialysis. The aim of this study was to analyze the predictive value of inflammatory parameters on mortality of continuous ambulatory peritoneal dialysis (CAPD) patients. Methods: Eighty-seven patients (57 males), aged from 30 to 85 [62.92 (10.61)] years who had been treated by a chronic program of CAPD for 3–113 months were analyzed. The basal period lasted 3 months with a follow-up of 30 months. Clinical parameters, dialysis adequacy and laboratory parameters including some inflammatory markers: serum amyloid-A (SAA), high sensitive C-reactive protein (hs-CRP), fibrinogen, erythrocyte sedimentation rate (ESR) and leukocytes were determined for each patient. Cox regression analysis selected the parameters of univariate and multivariate survival analysis. Results: During the follow-up period, 37 patients (42.5%) died. Univariate analysis selected the following potential mortality predictors (p < 0.10): age, months on CAPD, residual urine output, presence of cerebrovascular insult (CVI), KT/V, serum urea and albumin concentrations, SAA, hs-CRP, fibrinogen and ESR. In the multivariate survival analysis four models were created, each with a single inflammatory parameter. In all of these models, besides the age and CVI, inflammatory parameters were the most significant mortality predictors. When the inflammatory markers were analyzed altogether, multivariate analysis established that independent mortality predictors in this group of patients were: SAA, age and CVI. Conclusion: It may be concluded that in this studied group treated by CAPD, SAA was the most significant independent mortality predictor among the analyzed inflammatory markers.