Childhood-onset IgA nephropathy: is long-term recovery possible?

BACKGROUND: IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. While studies have primarily focused on identifying risk factors for disease progression, very few data exist on the likelihood of achieving complete recovery from the disease. METHODS: We conducted a single-center retrospective study on all consecutive patients with biopsy-proven IgAN diagnosed between 1986 and 2018 in our pediatric center. Biopsies were classified according to the MEST-C Oxford classification score. "Complete clinical remission" was defined as the absence of proteinuria, hematuria, and hypertension in patients with normal kidney function who had been off therapy for more than 2 years. RESULTS: Overall, 153 patients with age at onset of 10.6 ± 4 years were enrolled in the study. Of these, 41 achieved "complete clinical remission." The estimated probability of complete clinical remission at 10 years was 43% (95%CI 33-54). However, seven patients relapsed within 10 years. Multivariable analysis showed that higher age at onset (HR 0.89, 95%CI 0.80-0.98, p = 0.017) and segmental glomerulosclerosis lesions (HR 0.28, 95%CI 0.10-0.79, p = 0.017) decreased significantly the chances of achieving complete clinical remission. Immunosuppressive therapy was not significantly associated with clinical outcomes. CONCLUSIONS: Approximately one-third of patients with pediatric-onset IgAN achieve prolonged remission, in particular, very young children at disease onset without sclerotic glomerular lesions. Longer term follow-up is needed to assess if these patients have achieved permanent remission.

Impaired urinary concentration ability is a sensitive predictor of renal disease progression in Joubert syndrome.

BACKGROUND: Joubert syndrome (JS) is an inherited ciliopathy characterized by a complex midbrain-hindbrain malformation and multiorgan involvement. Renal disease, mainly juvenile nephronophthisis (NPH), was reported in 25-30% patients although only ∼18% had a confirmed diagnosis of chronic kidney disease (CKD). NPH often remains asymptomatic for many years, resulting in delayed diagnosis. The aim of the study was to identify a biomarker able to quantify the risk of progressive CKD in young children with JS. METHODS: Renal features were investigated in 93 Italian patients, including biochemical tests, ultrasound and 1-deamino-8D-arginine vasopressin test in children with reduced basal urine osmolality. A subset of patients was followed-up over time. RESULTS: At last examination, 27 of 93 subjects (29%) presented with CKD, ranging from isolated urinary concentration defect (UCD) to end-stage renal disease. Both normal and pathological urine osmolality levels remained stable over time, even when obtained at very early ages. Follow-up data showed that the probability of developing CKD can be modelled as a function of the urine osmolality value, exceeding 75% for levels <600 mOsm/kg H2O, and significantly increased in patients with an early diagnosis of isolated UCD. CONCLUSIONS: We conclude that the frequency of CKD in JS increases with age and is higher than previously reported. Urine osmolality represents an early sensitive quantitative biomarker of the risk of CKD progression.

Risk factors for progression in children and young adults with IgA nephropathy: an analysis of 261 cases from the VALIGA European cohort.

BACKGROUND: There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease. METHODS: Data on 261 young patients [age <23 years; mean follow-up of 4.9 (range 2.5-8.1) years] enrolled in VALIGA, a study designed to validate the Oxford Classification of IgAN, were assessed. Renal biopsies were scored for the presence of mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T1-2) (MEST score) and crescents (C1). Progression was assessed as end stage renal disease and/or a 50 % loss of estimated glomerular filtration rate (eGFR) (combined endpoint) as well as the rate of renal function decline (slope of eGFR). Cox regression and tree classification binary models were used and compared. RESULTS: In this cohort of 261 subjects aged <23 years, Cox analysis validated the MEST M, S and T scores for predicting survival to the combined endpoint but failed to prove that these scores had predictive value in the sub-group of 174 children aged <18 years. The regression tree classification indicated that patients with M1 were at risk of developing higher time-averaged proteinuria (p < 0.0001) and the combined endpoint (p < 0.001). An initial proteinuria of ≥0.4 g/day/1.73 m2 and an eGFR of <90 ml/min/1.73 m2 were determined to be risk factors in subjects with M0. Children aged <16 years with M0 and well-preserved eGFR (>90 ml/min/1.73 m2) at presentation had a significantly high probability of proteinuria remission during follow-up and a higher remission rate following treatment with corticosteroid and/or immunosuppressive therapy. CONCLUSION: This new statistical approach has identified clinical and histological risk factors associated with outcome in children and young adults with IgAN.

[Is it feasible to improve the duration and the efficiency of Ramipril anti-proteinuric response?]. / È possibile migliorare la durata e l'efficacia della risposta anti-proteinurica di Ramipril?

BACKGROUND: Ramipril administered once daily is characterized by an attenuation of its pharmacological activity in the following 24 hours, whose effects on antiproteinuric activity have not yet been investigated. METHODS: The antiproteinuric efficacy of Ramipril has been evaluated in a cross-over study in 20 patients with renal disease, proteinuria and hypertension (GFR50 mL / min, proteinuria <3 g / day; SBP/DBP 150/90 mmHg). Proteinuria was measured over 24 hours on three consecutive urine collections (morning, afternoon and night) in the absence of antiproteinuric drugs and after ten days of treatment with single morning administration of Ramipril 2.5 mg or Ramipril 10 mg. RESULTS: At baseline: mean proteinuria was not significantlychanged over the course of the three urinary collections (88 7.2 mg/h in the morning of 80 10.5 mg/h in the afternoon and 81 10.1 mg/hr during the night). After Ramipril 2.5 mg/day: slight reduction in mean proteinuria, with no significant differences between collections (80 11 mg/h in the morning, 69 7.4 mg/h in the afternoon and 75 9.1 mg/h during the night). After Ramipril 10 mg/day: afternoon and night values of proteinuria were significantly reduced compared to baseline; noctural proteinuria was significantly lower than morning value (51 7.5 mg/h vs. 81 10 mg/h, p <0.05). CONCLUSION: The antiproteinuric effectiveness of Ramipril tends to decrease significantly over the 24hours after a single daily administration. An increase and/or division of Ramipril dose might help to stabilize and to maximizeits antiproteinuric effectiveness.

Can renal sonography be a reliable diagnostic tool in the assessment of chronic kidney disease?

OBJECTIVES: Kidney size has been found to be correlated with anthropometric features and kidney function. Therefore, we postulate that if the conventionally measured renal sonographic parameters (pole-to-pole length, width, and parenchymal thickness) are taken according to standardized rules and corrected for body height, their association with kidney function could be strengthened, thus helping validate renal sonographic information for a better assessment of chronic kidney disease (CKD) status. METHODS: This cross-sectional study included 72 stable adult patients with stage 1 to 4 CKD. Sonographic parameters were obtained from both kidneys and averaged, and the measurements obtained were further corrected for patients' body height. The glomerular filtration rate (GFR) was estimated by the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: Parenchymal thickness and renal length showed the highest correlation level with the GFR. This significant correlation, however, was greatly ameliorated by the correction for patients' body height (r = 0.537; P < .001; r = 0.510; P < .001, respectively). Of note, the product of these two parameters corrected for body height showed the best degree of correlation with the GFR (r = 0.560; P < .001), as confirmed by analysis of variance after subdivision of the population into CKD stage groups according to the GFR. Receiver operating characteristic curve analysis for discrimination of a GFR of less than 60 mL/min indentified the combined parameter as the one with the highest area under the curve (0.78; 95% confidence interval, 0.66-0.89), followed renal length corrected for height (area under the curve, 0.77; 95% confidence interval, 0.66-0.88). CONCLUSIONS: Correction of renal sonographic parameters for body height strengthens the degree of the correlation of renal sonography with the GFR. The improved correlation with the GFR makes renal sonography a reliable tool for a more complete assessment of patients with CKD.

The kidney and the elderly: why does the risk increase?

Ageing is characterised by a decline in renal function and by a higher susceptibility to renal diseases. This has been defined by Fliser as the "myth of the inexorable decline of renal function with senescence" and is a consequence of multiple factors that predispose to renal damage. These include physiological factors that cannot be modified or treated, and pathological factors that can be treated and, sometimes, prevented; the former are represented by anatomic, molecular, and functional changes that physiologically occur during the ageing process; the latter-by acquired risk factors, whose incidence increases in the elderly, thus predisposing to or aggravating the renal damage. These include increased prevalence of age-related diseases, increased consumption of potentially nephrotoxic drugs, increased necessity of radiological procedures using iodinated contrast media, and increased necessity of major surgery. In this review we analyse these factors and their relevance in increasing the risk of renal damage in the elderly.

Renin-angiotensin system inhibitors reduce the progression of mesangioproliferative glomerulonephritis: 10 year follow-up.

BACKGROUND: Proteinuria is a common presentation of mesangioproliferative glomerulonephritis (MsPGN). No studies are available on the long-term effect of treatment by renin-angiotensin system (RAS) inhibitors on renal outcome in MsPGN patients. This study prospectively evaluates the effects of RAS inhibitors on renal outcome in patients with low risk MsPGN followed up for 10 years using historical patients with similar features at the time of presentation as untreated controls. ENDPOINTS: decrease of basal proteinuria>20% and loss>20% of basal glomerular filtrate rate (GFR) at the end of first year of observation. The patients were re-evaluated bimonthly during the first year and every 6 months thereafter. RESULTS: Twenty-five patients fulfilled the selection criteria. After one year follow-up 19 patients reached the endpoint of proteinuria and no patient reached the endpoint of GFR. No significant change in blood pressure levels (BP) and GFR was registered, by contrast daily proteinuria decreased significantly (p<0.001), falling by 29% at sixth month and 47% at the end of the follow-up. The historical control group consisted of 15 untreated patients seen between 1987 and 1992. The two-way analysis of variance for repeated measures showed greater values of GFR (p<0.001) and lower levels of daily proteinuria (p<0.001) in treated patients as compared to untreated controls. CONCLUSIONS: This 10-year follow-up study indicates that the early treatment with RAS inhibitors at low doses favourably influences the long-term renal outcome in proteinuric patients with MsPGN. Limitations were the small sample size and lack of randomization.

Cool temperature hemodialysis and biocompatibility in chronic hemodialysis patients: a preliminary study.

BACKGROUND: Cooler temperature dialysate (TD) has gained in popularity in the treatment of hypotension during hemodialysis (HD). In this study we verified the hypothesis of an eventual involvement of cytokines. METHODS: Four patients on regular HD underwent two 4-hour HD sessions once at 37 degrees C TD and once at 35 degrees C TD. The concentration of the cytokines (cyt) IL-1, IL-2, IL-8, IL-12 and tumor necrosis factor-alpha (TNF-alpha) was measured before the HD session initiation and after 20, 60, 120 and 240 minutes. Body temperature, weight, blood pressure and heart rate were registered at the same time points. RESULTS: We found a higher blood pressure at 35 degrees C but no intradialytic differences in cyt concentration at 35 degrees C or 37 degrees C. The percentage changes of cyt from baseline were very slight, except for IL-8 which decreased by 40% both at 35 degrees C and 37 degrees C. CONCLUSIONS: These preliminary results suggest that cytokines do not seem play a relevant role in determining the favorable effects of cooler TD on blood pressure. Our study is preliminary and our results need to be confirmed by other studies.

Can pulsatile cardiopulmonary bypass prevent perioperative renal dysfunction during myocardial revascularization in elderly patients?

BACKGROUNDS/AIMS: We recently demonstrated that pulsatile cardiopulmonary bypass (CPB) versus standard linear CPB is associated with better perioperative renal function. Since older subjects have a higher risk of acute renal failure, we have extended our study to evaluate the specific impact of pulsatile CPB on the perioperative renal function in elderly patients. METHODS: We enrolled 50 patients with normal preoperative renal function: they were stratified by age (65-75 vs. 50-64 years) and randomized to nonpulsatile (group A) or pulsatile CPB (group B). Twenty-seven patients aged > or =50 years and <65 years were randomized to group A (n = 12) or to group B (n = 15) and 23, aged > or =65 years and < or =75 years, to group A (n = 13) or to group B (n = 10). Glomerular filtrate rate (GFR), daily diuresis, lactatemia and other parameters were measured during the pre- and perioperative period. RESULTS: The percent perioperative decrease in GFR was lower in group A than in group B (p < 0.001), without differences between older and younger patients. By contrast, perioperative plasma lactate levels were higher in group A than in group B (p < 0.001), both in older and younger patients. No difference was observed for 24 h urine output and blood urea nitrogen. CONCLUSIONS: Pulsatile CPB preserves renal function better than standard CPB even in patients older than 65. CPB could be adopted as the procedure of choice in this subgroup of patients.

Dyspeptic symptoms in children: the result of a constipation-induced cologastric brake?

BACKGROUND & AIMS: Patients with constipation frequently complain of dyspeptic symptoms that may be explained by reflex inhibition of upper-gastrointestinal motor activity by colonic stimuli. We sought to evaluate the following: (1) the prevalence of functional constipation (FC) and gastric emptying characteristics in children with functional dyspepsia (FD), and (2) the efficacy of osmotic laxatives on constipation, dyspeptic symptoms, and gastric motility. METHODS: We recruited 42 children (males/females, 22/20; mean age, 80.5 mo) affected by FD (Rome II criteria). All subjects underwent ultrasonographic measurement of the total gastric emptying time (TGEt) at baseline (T0) and after 3 months (T3). Children's bowel habits and the dyspeptic symptomatic score were evaluated at entry and after 1 (T1), 2 (T2), and 3(T3) months. Constipated patients were treated with osmotic laxatives for 3 months. Dyspeptic children without constipation represented the comparison group. RESULTS: FC was present in 28 of 42 (66.6%) patients. Constipated dyspeptic children had significantly more prolonged TGEt than subjects without constipation (median value [interquartile range], 180 (50) vs 150 (28) min, respectively; P = .004). Patients on osmotic laxatives had a significant decrease in TGEt at 3 months (P < .001). The median dyspeptic symptomatic score as well as the number and consistency of evacuations per week significantly improved at T1 in comparison with T0 and even more at T2 and T3 (P < .001, for each). CONCLUSIONS: In our study group, the majority of children with FD were affected by FC associated with delayed gastric emptying. Normalization of bowel habit may improve gastric emptying as well as dyspeptic symptoms.

Can young adult patients with proteinuric IgA nephropathy perform physical exercise?

BACKGROUND: It is not known whether physical exercise increases daily proteinuria in patients with proteinuric nephropathies, thus accelerating progression of the renal lesion. This study evaluates the acute effects of physical exercise on proteinuria in young adults with immunoglobulin A (IgA) nephropathy. METHODS: Changes induced by intense physical exercise on quantitative and qualitative proteinuria were evaluated in basal conditions and after 10 days of ramipril therapy in 10 patients with IgA nephropathy, normal glomerular filtration rate (GFR), proteinuria between 0.8 and 1.49 g/24 h, and "glomerular" microhematuria before and after the end of a maximal treadmill Bruce test (B-test). The basal study also was performed in 10 age- and sex-matched healthy volunteers. RESULTS: At rest, GFR averaged 141 +/- 23 mL/min; it increased by 16.3% +/- 3.3% (P < 0.005) and 7.1% +/- 1.6% at 60 and 120 minutes after the B-test, respectively. At rest, GFR-corrected proteinuria averaged protein of 0.76 +/- 0.21 mg/min/100 mL GFR; it increased to 1.55 +/- 0.28 mg/min/100 mL GFR after 60 minutes (P < 0.001) and declined to 0.60 +/- 0.11 mg/min/100 mL GFR at 120 minutes after the end of the B-test. The pattern of urinary proteins remained unchanged, as did microhematuria. Daily proteinuria was not different from the basal value on the day of the B-test. After ramipril therapy, patients showed a reduction in GFR, but no change in daily GFR-corrected proteinuria, pattern of urinary proteins, or hematuria. CONCLUSION: The increase in proteinuria after exercise in our patients is significant and is not prevented by ramipril therapy, but lasts less than 120 minutes. Therefore, it cannot modify daily proteinuria. Thus, these data do not support the need to reduce acute physical activity in patients with nonnephrotic renal diseases.