Autosomal dominant polycystic kidney disease in young adults.

Background: The clinical manifestations of autosomal dominant polycystic kidney disease (ADPKD) usually appear in adulthood, however pediatric series report a high morbidity. The objective of the study was to analyze the clinical characteristics of ADPKD in young adults. Methods: Family history, hypertension, albuminuria, estimated glomerular filtration rate (eGFR) and imaging tests were examined in 346 young adults (18-30 years old) out of 2521 patients in the Spanish ADPKD registry (REPQRAD). A literature review searched for reports on hypertension in series with more than 50 young (age <30 years) ADPKD patients. Results: The mean age of this young adult cohort was 25.24 (SD 3.72) years. The mean age at diagnosis of hypertension was 21.15 (SD 4.62) years, while in the overall REPQRAD population was aged 37.6 years. The prevalence of hypertension was 28.03% and increased with age (18-24 years, 16.8%; 25-30 years, 36.8%). Although prevalence was lower in women than in men, the age at onset of hypertension (21 years) was similar in both sexes. Mean eGFR was 108 (SD 21) mL/min/1.73 m2, 38.0% had liver cysts and 3.45% of those studied had intracranial aneurysms. In multivariate analyses, hematuria episodes and kidney length were independent predictors of hypertension (area under the curve 0.75). The prevalence of hypertension in 22 pediatric cohorts was 20%-40%, but no literature reports on hypertension in young ADPKD adults were found. Conclusions: Young adults present non-negligible ADPKD-related morbidity. This supports the need for a thorough assessment of young adults at risk of ADPKD that allows early diagnosis and treatment of hypertension.

Infección del tracto urinario en la enfermedad renal crónica / Urinary tract infection in chronic kidney disease patients

Resumen Las infecciones en personas con enfermedad renal crónica son una causa importante de morbimortalidad. Los pacientes renales presentan factores de riesgo específicos para la adquisición de infecciones, que además suelen ser más graves, de progresión más rápida y de resolución más lenta que en sujetos sanos. La infección del tracto urinario en esta población es a menudo complicada debido a la presencia de diabetes, microorganismos multirresistentes, anomalías anatómicas o funcionales del tracto urinario, alteraciones metabólicas y el uso frecuente de sonda vesical. Las infecciones urinarias ocasionan una de las tasas más altas de hospitalización en diálisis y son muy prevalentes en el trasplante renal. Este trabajo tiene como objetivo revisar la literatura publicada sobre la etiología, el diagnóstico microbiológico y el tratamiento de las infecciones del tracto urinario en pacientes con enfermedad renal crónica.

Abstract Infections in chronic kidney disease patients are a major cause of morbidity and mortality. Renal patients have specific risk factors for acquiring infections, which also tend to be more severe and have a more rapid progression and slower resolution than in the healthy individuals. Urinary tract infection in renal patients is often complicated due to the presence of diabetes, multiresistant microorganisms, anatomic or functional abnormalities of the urinary tract, metabolic disturbances and the frequent use of urinary catheters. It causes one of the highest rates of hospitalization among dialysis patients and is highly prevalent in kidney transplantation. The aim of this work is to review the etiology, microbiological diagnosis and treatment of urinary tract infections in chronic kidney disease patients.

Therapeutic variability in adult minimal change disease and focal segmental glomerulosclerosis.

BACKGROUND: Variability in the management of glomerulonephritis may negatively impact efficacy and safety. However, there are little/no data on actual variability in the treatment of minimal change disease (MCD)/focal segmental glomerulosclerosis (FSGS) in adults. We assessed Spanish practice patterns for the management of adult nephrotic syndrome due to MCD or FSGS. The absence of reasonably good evidence on treatment for a disease often increases the variability substantially. Identification of evidence-practice gaps is the first necessary step in the knowledge-to-action cyclical process. We aim to analyse the real clinical practice in adults in hospitals in Spain and compare this with the recently released Kidney Disease: Improving Global Outcomes clinical practice guideline for glomerulonephritis. METHODS: Participating centres were required to include all adult patients (age >18 years) with a biopsy-proven diagnosis of MCD or FSGS from 2007 to 2011. Exclusion criteria included the diagnosis of secondary nephropathy. RESULTS: We studied 119 Caucasian patients with biopsy-proven MCD (n = 71) or FSGS (n = 48) from 13 Spanish hospitals. Of these patients, 102 received immunosuppressive treatment and 17 conservative treatment. The initial treatment was steroids, except in one patient in which mycophenolate mofetil was used. In all patients, the steroids were given as a single daily dose. The mean duration of steroid treatment at initial high doses was 8.7 ± 13.2 weeks and the mean global duration was 38 ± 32 weeks. The duration of initial high-dose steroids was <4 weeks in 41% of patients and >16 weeks in 10.5% of patients. We did find a weak and negative correlation between the duration of whole steroid treatment in the first episode and the number of the later relapses (r = -0.24, P = 0.023). There were 98 relapses and they were more frequent in MCD than in FSGs patients (2.10 ± 1.6 versus 1.56 ± 1.2; P = 0.09). The chosen treatment was mainly steroids (95%). Only seven relapses were treated with another drug as a first-line treatment: two relapses were treated with mycophenolate and five relapses were treated with anticalcineurinics. A second-line treatment was needed in 29 patients (24.4%), and the most frequent drugs were the calcineurin inhibitors (55%), followed by mycophenolate mofetil (31%). Although cyclophosphamide is the recommended treatment, it was used in only 14% of the patients. CONCLUSIONS: We found variation from the guidelines in the duration of initial and tapered steroid therapy, in the medical criteria for classifying a steroid-resistant condition and in the chosen treatment for the second-line treatment. All nephrologists started with a daily dose of steroids as the first-line treatment. The most frequently used steroid-sparing drug was calcineurin inhibitors. Cyclophosphamide use was much lower than expected.

Decreasing incidence of AA amyloidosis in Spain.

BACKGROUND: The main objectives of our study were to review all cases of amyloidosis diagnosed by renal biopsy in Spain from 1994 to 2009 and to analyse variations in the incidence over time. MATERIALS AND METHODS: We analysed all biopsies from native kidneys included in the Spanish Registry of Glomerulonephritis. A total of 120 centres provided 17 680 biopsies over 16 years. Follow-up was divided in four periods. RESULTS: We collected 653 cases of renal amyloidosis. In 438 cases (67%), amyloidosis type was specified, [AA amyloidosis, 253 cases (57·8%); AL amyloidosis, 185 cases (42·2%)]. Mean age was 60 (17·8) years; 51·4% of patients were younger than 65. Overall incidence was 3·7%. In patients < 65, AA amyloidosis was present in 66·1% and AL amyloidosis in 33·9% (P < 0·01). No differences were found in patients > 65. Patients with AA amyloidosis were younger (56·8 vs. 64·0, P < 0·01) and had worse creatinine clearance (35 vs. 57 mL/min, P < 0·01). We found a decrease in the incidence among biopsies collected during each of the 4 study periods (4·2%, 3·9%, 3·5% and 3·2%, respectively, P < 0·001). CONCLUSIONS: This is the largest series of renal amyloidosis in kidney biopsies published to date. We found amyloidosis to be decreasing slowly in Spain. This decrease affects both types and is confirmed in all cases marked in patients < 65 and in AA type. AA amyloidosis was the most frequent in our series. Patients affected by it were younger and had worse kidney function, with no differences in the level of proteinuria.

Intraindividual interleukin-6 variations on the cardiovascular prognosis of patients with chronic renal disease.

In chronic kidney disease (CKD) patients on dialysis, plasma interleukin (IL)-6 levels predict mortality better than other markers. Impact of intraindividual changes of inflammatory markers on cardiovascular (CV) events in CKD patients is unknown. The aim of this study is to demonstrate the relation between CV outcomes and variations of C-reactive protein (CRP), IL-6, IL-1ß, and tumor necrosis factor (TNF)-α in CKD. Ninety patients (mean age: 68.5 ± 12.8 years) at different stages (1-4) of CKD were evaluated. Serum CRP, IL-6, IL-1ß, and TNF-α were measured basally and after taking statins or angiotensin II receptor blockers. Three patterns were defined for each marker (baseline, mean of two measurements, and variation of the marker: increase or decrease after 6 months). During follow-up (mean time: 72.7 ± 19.8 months), 14 patients died, 11 were included on dialysis program, and 29 suffered a CV event. Patients with persistently elevated IL-6 values had higher risk to develop CV events [OR = 1.21 (1.11-1.32), p = 0.001]. Mean of two measurements of IL-6 was a better predictor for events than a single measurement of IL-6, CRP, TNF-α, and IL-1ß. A mean of two determinations of plasma IL-6 greater than 6 pg/mL and previous peripheral vascular disease was related to an increased risk for CV events [2.34 (1.05-5.22), p = 0.037 and 2.95 (1.27-6.93), p = 0.011, respectively] in an adjusted Cox regression model. IL-6 is a better inflammatory marker than CRP, TNF-α, and IL1ß at predicting CV events in CKD nondialysis patients. Mean of two measurements is better than simple determinations at predicting CV outcome.

Effects of pentoxifylline on inflammatory parameters in chronic kidney disease patients: a randomized trial.

BACKGROUND: Pentoxifylline (PTF) is a potential therapeutic agent in chronic kidney disease due to its antiinflammatory and antiproteinuric effects that may influence the progression of renal disease. SUBJECTS AND METHODS: We conducted a prospective randomized trial of 91 patients with estimated glomerular filtration rate (eGFR) <60 ml/min, calculated with 4-variable Modification of Diet in Renal Disease (MDRD-4) Study equation. Patients were randomly assigned to treatment with PTF 400 mg (twice a day) (n=46) or to continue their usual therapy (n=45). Clinical, biochemical and inflammatory parameters were measured at baseline, and at 6 and 12 months of treatment. The objective of the study was to analyze the effect of PTF treatment on inflammatory markers and secondarily the effect on renal disease progression. RESULTS: Baseline characteristics were similar in the 2 groups. High-sensitivity C-reactive protein (hs-CRP), serum fibrinogen and TNF-alpha decreased significantly in patients treated with PTF in comparison with the control group at 12 months (p=0.002, p=0.001 and p=0.000, respectively). Median urinary albumin excretion did not decrease with PTF treatment. In the PTF group, there was no significant change in eGFR after 12 months (from 42.3 ± 10.2 to 44.7 ± 11.3 ml/min per 1.73 m(2)), whereas in the control group there was a worsening by the end of the study (from 40.1 ± 12.4 to 35.7 ± 13.4 ml/min per 1.73 m(2)) (p=0.000 between groups). CONCLUSIONS: PTF treatment decreases inflammatory markers in chronic kidney disease and stabilizes renal function.