Significance of clinical and morphological prognostic risk factors in IgA nephropathy: follow-up study of comparison patient groups with and without renoprotection.

BACKGROUND: IgA nephropathy (IgAN) is the most frequent glomerulonephritis in many countries including Estonia. There is no specific treatment for IgAN but renoprotection is indicated when proteinuria is >1 g/day. We aimed to assess the clinicopathological correlations of IgAN and to compare the follow-up outcome of the IgAN patients receiving renoprotection with the patients with other antihypertensive regimen treatments. METHODS: A retrospective kidney biopsy cohort study was carried out in consecutive 73 IgAN cases, using the new Oxford classification. The baseline and follow-up (FU, 4.1 years) clinical data were collected. The patients were divided into two main study groups according to their drug-treatment: the drug-treated and untreated patients' groups. Two subgroups among patients receiving two different antihypertensive drugs were formed and statistically analysed: Renin-angiotensin system (RASb, renoprotection) - and calcium-channel blockers (CCB)-receiving patients. Also, patient' subgroups with and without the presence of clinical and morphological risk factors were used for statistical analysis. RESULTS: The patients' mean age was 33.7 years (range 16-76). Proteinuria decreased at the end of FU (0.91 g/24 h to 0.79 g/24 h). Mean arterial pressure remained at the end of FU almost at the same level. Drug treatment was prescribed to the patients who had lower eGFR, higher proteinuria and more severe histological lesions (S1, T1/2), while the patients with minimal clinical symptoms and the ones with near-normal kidney function remained without drug treatment. The kidney function remained almost at the same normal level in untreated patients irrespective of the risk factors whereas in both treated patient' subgroups eGFR declined. The following statistically significant correlations in the IgAN cohort were found: correlations in patients with lower kidney function (eGFR <60 ml/min/1.73 m2), higher blood pressure (p = 0.00006) and proteinuria were found irrespectively of the fact whether the patients received (p = 0.006) or did not receive renoprotection (p = 0.001). The biggest significant eGFR change by Wilcoxon rank sum test was found among the patients who had clinical and morphological risk factors and received treatment. The result was confirmed by post hoc analysis and did not depend on the presence of treatment. In the investigation of the subgroups receiving RASb we found that the lowering of eGFR did depend on the presence of clinical and morphological risk factors. CONCLUSIONS: Renoprotection is only effective in preventing the progression of IgAN when clinical and morphological risk factors are modest or missing.

IgA nephropathy clinicopathologic study following the Oxford classification: Progression peculiarities and gender-related differences.

BACKGROUND AND AIM: Immunoglobulin A nephropathy (IgAN) is the most frequent glomerular disease worldwide and one of the main causes of chronic kidney disease. We aimed to investigate clinicopathological correlations in IgAN patients by gender. MATERIALS AND METHODS: The study was based on a retrospective analysis of renal biopsy data and clinical manifestations of the disease. Consecutive 73 biopsy-proven IgAN cases of male (62%) and female (38%) patients were investigated. Renal biopsies were reviewed using the new Oxford classification assessing the MEST (mesangial hypercellularity, endocapillary hypercellularity, segmental sclerosis/adhesion, tubular atrophy/interstitial fibrosis) score. The most powerful IgAN prognostic risk factors, morphological (segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis) as well as clinical (proteinuria and hypertension) were taken into account in the correlation analysis. The mean rate of renal function decline was expressed as a slope of eGFR during the follow-up (FU) dividing delta GFR with the FU years. RESULTS: The mean age of the patients was 33.7 years (range, 16-76). Follow-up data were available for 64 patients with the mean follow-up of 4.1 years. The mean proteinuria at biopsy was 0.79g/24h. The mean arterial pressure (MAP) was 94.5±16.7mmHg and 7% of the patients were hypertensive. The initial mean estimated glomerular filtration rate (eGFR) was 94.9±30.7mL/min, at the end of the follow-up it was 86.2±27.1mL/min. The mean rate of renal function decline was -3.4±11.9mL/min/1.73m2 per year in males (P<0.05) and -0.7±5.3mL/min/1.73m2 per year in females. The Spearman correlation analysis confirmed a higher MEST score in the whole cohort and in males correlated with disease progression. In patients with proteinuria below 1.0g/24h, disease progression was faster in males. CONCLUSIONS: According to the correlation analysis of the main prognostic risk factors, affecting the progression of IgAN, we can conclude that IgA nephropathy in males progresses more rapidly compared to females.

Improvements in renal replacement therapy practice patterns in estonia.

BACKGROUND: The clinical performance indicators (CPI) are important tools to assess and improve the quality of renal replacement therapy (RRT). The aim of the current study was to compare the results of a longitudinal set of CPI in RRT patients and to determine the extent to which the guidelines for anaemia, calcium phosphate management and other CPI are met in Estonian renal centres. METHODS: A long-term retrospective, observational, cross-sectional CPI analysis was undertaken in RRT patients from 2007 to 2011. The following CPI set of well-designed measures based on good evidence was analysed: anaemia management variables, laboratory analyses of mineral metabolism, nutritional status variables and dialysis adequacy variables. RESULTS: Relatively small changes in the analysed mean CPI values were noticed during the study period. In the course of the study, we noticed an improvement in anaemia control, but not all centres achieved the standard of >80% of the dialysis patients with a haemoglobin (Hb) level >100 g/l. There was a trend of decreasing Hb concentrations below 125 g/l in both haemodialysis (HD) and peritoneal dialysis (PD) patients. In 2011, hyperphosphataemia was present in 58% of the HD and 47% of the PD patients, whereas centre differences varied between 50 and 60% of both the HD and PD patients. HD adequacy was achieved in 77% of the HD patients. CONCLUSION: An improvement in the data collection was noticed, and the analysis of CPI allows renal centres to assess and compare their practices with others. The collection and evaluation of CPI of RRT patients is an important improvement and significantly increases the awareness of nephrologists.

Genetic characterization of hepatitis C virus strains in Estonia: fluctuations in the predominating subtype with time.

During the last decade, there has been a dramatic increase in intravenous drug use in young adults in Estonia with an increased incidence of both hepatitis B and C as a consequence. Since genetic data are limited regarding hepatitis C virus (HCV) strains in Estonia, the aim of the study was to characterize HCV strains in different risk groups to determine their relatedness to strains from other geographical regions. Three hundred fifty-three anti-HCV positive sera collected during 1994-2004 from hospitalized patients, blood donors and health care workers were used as source of HCV RNA. Two hundred nine (59%) of the sera were positive for HCV RNA by PCR directed to the 5'-UTR region. For 174 strains the HCV subtype was determined by analyses of the NS5B and/or the 5'UTR-core regions. 1b (71%) was the most common subtype followed by 3a (24%), 2c (2%), 1a (1%), and 2a (1%). The 1b and 3a strains were similar to strains from other regions of the former USSR. Within genotype 1b there were several HCV lineages. However, for 3a there seemed to be two separate introductions into Estonia. There was a relative shift from subtype 1b to 3a in 1999-2000 with a further replacement of 3a with 1b in intravenous drug users in 2001 and onwards (P < 0.05). However, both subtypes were found to co-circulate in the community independent of risk factors. One patient was infected with the 2k/1b recombinant presumed to originate from St. Petersburg being the first isolate of this recombinant recovered outside Russia.

Successful rescue therapy with mycophenolate mofetil in kidney transplantation improves the long-term graft survival.

OBJECTIVE: The aim of this study was to compare the graft survival after kidney transplantation in patients treated with azathioprine (AZA) or mycophenolate mofetil (MMF) and analyze the significance of different risk factors for graft survival. MATERIAL AND METHODS: A total of 137 patients, transplanted between January 1996 and June 2001, were retrospectively divided into two groups: patients who received AZA together with cyclosporine A and methylprednisolone (AZA group, n=72) and patients who received MMF either immediately or were switched from AZA to MMF during 3 months (MMF group, n=65). RESULTS: According to Kaplan-Meier analysis, a 1-year graft survival was 79% in the AZA group and 85% in the MMF group; a 6-year graft survival was 51% and 67%, respectively (P=0.046). Multivariate Cox survival model demonstrated that MMF therapy reduced the risk of graft loss by 34% (P=0.028), while delayed graft function increased the risk of graft loss (risk ratio 2.26, P=0.009). A statistically significant difference in total cholesterol level (6.7 vs. 5.7 mmol/L, respectively; P=0.002), mean systolic blood pressure (145 vs. 134 mmHg, P=0.009), and cyclosporine A daily dose (238 vs. 203 mg, P=0.015) between the AZA and MMF groups at 1 year was revealed. CONCLUSION: MMF rescue therapy improves the long-term graft survival compared to AZA despite high early rejection rate and avoids the negative impact of acute rejections on graft survival.