Suboptimal dialysis initiation is associated with comorbidities and uraemia progression rate but not with estimated glomerular filtration rate.

BACKGROUND: Despite early referral of uraemic patients to nephrological care, suboptimal dialysis initiation (SDI) remains a common problem associated with increased morbimortality. We hypothesized that SDI is related to pre-dialysis care. METHODS: In the 'Peridialysis' study, time and reasons for dialysis initiation (DI), clinical and biochemical data and centre characteristics were registered during the pre- and peri-dialytic period for 1583 end-stage kidney disease patients starting dialysis over a 3-year period at 15 nephrology departments in the Nordic and Baltic countries to identify factors associated with SDI. RESULTS: SDI occurred in 42%. Risk factors for SDI were late referral, cachexia, comorbidity (particularly cardiovascular), hypoalbuminaemia and rapid uraemia progression. Patients with polycystic renal disease had a lower incidence of SDI. High urea and C-reactive protein levels, acidosis and other electrolyte disorders were markers of SDI, independently of estimated glomerular filtration rate (eGFR). SDI patients had higher eGFR than non-SDI patients during the pre-dialysis period, but lower eGFR at DI. eGFR as such did not predict SDI. Patients with comorbidities had higher eGFR at DI. Centre practice and policy did not associate with the incidence of SDI. CONCLUSIONS: SDI occurred in 42% of all DIs. SDI was associated with hypoalbuminaemia, comorbidity and rate of eGFR loss, but not with the degree of renal failure as assessed by eGFR.

Is there long-term value of pathology scoring in immunoglobulin A nephropathy? A validation study of the Oxford Classification for IgA Nephropathy (VALIGA) update.

BACKGROUND: It is unknown whether renal pathology lesions in immunoglobulin A nephropathy (IgAN) correlate with renal outcomes over decades of follow-up. METHODS: In 1130 patients of the original Validation Study of the Oxford Classification for IgA Nephropathy (VALIGA) cohort, we studied the relationship between the MEST score (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T), crescents (C) and other histological lesions with both a combined renal endpoint [50% estimated glomerular filtration rate (eGFR) loss or kidney failure] and the rate of eGFR decline over a follow-up period extending to 35 years [median 7 years (interquartile range 4.1-10.8)]. RESULTS: In this extended analysis, M1, S1 and T1-T2 lesions as well as the whole MEST score were independently related with the combined endpoint (P < 0.01), and there was no effect modification by age for these associations, suggesting that they may be valid in children and in adults as well. Only T lesions were associated with the rate of eGFR loss in the whole cohort, whereas C showed this association only in patients not treated with immunosuppression. In separate prognostic analyses, the whole set of pathology lesions provided a gain in discrimination power over the clinical variables alone, which was similar at 5 years (+2.0%) and for the whole follow-up (+1.8%). A similar benefit was observed for risk reclassification analyses (+2.7% and +2.4%). CONCLUSION: Long-term follow-up analyses of the VALIGA cohort showed that the independent relationship between kidney biopsy findings and the risk of progression towards kidney failure in IgAN remains unchanged across all age groups and decades after the renal biopsy.

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.

Adverse lifestyle and health-related quality of life: gender differences in patients with and without chronic conditions.

OBJECTIVES: The aim was to investigate the relationship between the main lifestyle-related factors and health-related quality of life (HRQoL) in a sample of patients with and without chronic conditions (CCs) with respect to the gender differences in both groups. METHODS: A cross-sectional study was conducted on 1061 patients (of which 308 had no CCs and 753 of those had one or more CCs) recruited at primary health care centres and the Internal Medicine Clinic at Tartu University Hospital in Estonia. Data were collected during 2012-2014. The patient's age, self-reported smoking status, alcohol consumption (assessed by Alcohol Use Disorders Identification Test) and body mass index were used as independent variables to predict the physical component scores (PCS) and mental component scores (MCS) of HRQoL (assessed by SF-36). RESULTS: Smoking had a negative association with both physical and mental components of HRQoL only in women with CCs. Further, the PCS of chronically ill women was negatively associated with the higher body mass index. Harmful drinking had a negative association with the HRQoL in all patient groups, except with the PCS in women with CC. Light alcohol consumption without symptoms of harmful use or dependency had a positive association with the physical and mental HRQoL in all patient groups, except with the MCS in women without CCs. CONCLUSION: Adverse lifestyle had the most expressed association with HRQoL in women with CCs. Light alcohol consumption had a positive association, but harmful use of alcohol had an inverse association with HRQoL irrespective of patients' gender or health status.

Tonsillectomy in a European Cohort of 1,147 Patients with IgA Nephropathy.

BACKGROUND: Tonsillectomy has been considered a treatment for IgA nephropathy (IgAN). It is aimed at removing a source of pathogens, reducing mucosa-associated lymphoid tissue and decreasing polymeric IgA synthesis. However, its beneficial effect is still controversial. In Asia, favorable outcomes have been claimed mostly in association with corticosteroids. In Europe, small, single-center uncontrolled studies have failed to show benefits. METHODS: The European validation study of the Oxford classification of IgAN (VALIGA) collected data from 1,147 patients with IgAN over a follow-up of 4.7 years. We investigated the outcome of progression to end-stage renal disease (ESRD) and/or 50% loss of estimated glomerular filtration rate (eGFR) and the annual loss of eGFR in 61 patients who had had tonsillectomy. RESULTS: Using the propensity score, which is a logistic regression model, we paired 41 patients with tonsillectomy and 41 without tonsillectomy with similar risk of progression (gender, age, race, mean blood pressure, proteinuria, eGFR at renal biopsy, previous treatments and Oxford MEST scores). No significant difference was found in the outcome. Moreover, we performed an additional propensity score pairing 17 patients who underwent tonsillectomy after the diagnosis of IgAN and 51 without tonsillectomy with similar risk of progression at renal biopsy and subsequent treatments. No significant difference was found in changes in proteinuria, or in the renal end point of 50% reduction in GFR and/or ESRD, or in the annual loss of eGFR. CONCLUSION: In the large VALIGA cohort of European subjects with IgAN, no significant correlation was found between tonsillectomy and renal function decline.

Occurrence of kidney diseases and patterns of glomerular disease based on a 10-year kidney biopsy material: a retrospective single-centre analysis in Estonia.

OBJECTIVE: Kidney biopsy is an important diagnostic tool in assessing glomerular damage. This study aimed to determine the occurrence of glomerular disease during the past decade at a single centre, to assess potential changes in the structure of primary glomerulopathies over time, and to define gender- and age-related differences. MATERIAL AND METHODS: A total of 578 consecutive native kidney biopsies during the period 2000-2010 was retrospectively reviewed at Tartu University Hospital, Estonia. Biopsies were evaluated according to clinical data with standard histological methods. RESULTS: The patients' mean age was 39.9 ± 17.9 (range 4-87) years. Less than half of informative kidney biopsies (n = 547) comprised primary glomerulopathies (45.4%), the patients' mean age was 38.7 ± 17.7 (4-79) years and the predominant group comprised male patients. Secondary glomerulopathies made up 22.3%, tubulointerstitial diseases 8.2% and other conditions 24.1%. Among primary glomerulopathies, inflammatory damage to glomeruli dominated (63.4%), whereas immunoglobulin A (IgA) nephropathy was the most common disease (35.5%). Non-inflammatory diseases of glomeruli made up 34.6%, among which the most common was focal and segmental glomerulosclerosis (16.1%), followed by minimal change disease (14.1%). Membranoproliferative glomerulonephritis was a rare form of glomerular damage among primary glomerulopathies (7.7%). Comparison between male and female cases in the primary glomerulopathies group revealed a statistically significant difference in their frequency (p = 0.01). CONCLUSIONS: Inflammatory glomerulopathies mostly prevailed in the spectrum of primary glomerulopathies. IgA nephropathy was the most common glomerulopathy. Comparing the data with those from a 15-year earlier period at the same centre, a change towards non-inflammatory glomerulopathies was noticed.