The coexistence of diabetic retinopathy and diabetic nephropathy is associated with worse kidney outcomes.

Background: Up to 50-60% of patients with diabetes have non-diabetic kidney disease (NDKD) on kidney biopsy. Diabetic retinopathy (DR) is a microvascular complication of diabetes frequently associated with diabetic nephropathy (DN). The objective of the current study was to investigate the kidney outcomes and survival in patients with biopsy diagnoses of DN and NDKD according to the presence of DR. Methods: We conducted an observational, multicentre and retrospective study of the pathological findings of renal biopsies from 832 consecutive patients with diabetes from 2002 to 2014 from 18 nephrology departments. The association of DR with kidney replacement therapy (KRT) or survival was assessed by Kaplan-Meier and Cox regression analyses. Results: Of 832 patients with diabetes and renal biopsy, 768 had a retinal examination and 221/768 (22.6%) had DR. During a follow-up of 10 years, 288/760 (37.9%) patients with follow-up data needed KRT and 157/760 (20.7%) died. The incidence of KRT was higher among patients with DN (alone or with NDKD) and DR [103/175 (58.9%)] than among patients without DR [88/216 (40.7%), P < .0001]. The incidence of KRT was also higher among patients with only NDKD and DR than among those without DR [18/46 (39.1%) versus 79/331 (23.9%), P < .0001]. In multivariate analysis, DR or DN were independent risk factors for KRT {hazard ratio [HR] 2.48 [confidence interval (CI) 1.85-3.31], P < .001}. DN (with or without DR) was also identified as an independent risk factor for mortality [HR 1.81 (CI 1.26-2.62), P = .001]. Conclusions: DR is associated with a higher risk of progression to kidney failure in patients with histological DN and in patients with NDKD.

Effect of Immunosuppressive Treatments on Kidney Outcomes After Gross Hematuria-Related Acute Kidney Injury in Older Patients With IgA Nephropathy.

Introduction: Macroscopic hematuria (MH) bouts, frequently accompanied by acute kidney injury (AKI-MH) are one of the most common presentations of IgA nephropathy (IgAN) in the elderly. Immunosuppressive therapies are used in clinical practice; however, no studies have analyzed their efficacy on kidney outcomes. Methods: This is a retrospective, multicenter study of a cohort of patients aged ≥50 years with biopsy-proven IgAN presenting with AKI-MH. Outcomes were complete, partial, or no recovery of kidney function at 1 year after AKI-MH, and kidney survival at 1, 2, and 5 years. Propensity score matching (PSM) analysis was applied to balance baseline differences between patients treated with immunosuppression and those not treated with immunosuppression. Results: The study group consisted of 91 patients with a mean age of 65 ± 15 years, with a mean follow-up of 59 ± 36 months. Intratubular red blood cell (RBC) casts and acute tubular necrosis were found in all kidney biopsies. The frequency of endocapillary hypercellularity and crescents were low. Immunosuppressive therapies (corticosteroids alone or combined with mycophenolate mofetil or cyclophosphamide) were prescribed in 52 (57%) patients, whereas 39 (43%) received conservative treatment. There were no significant differences in the proportion of patients with complete, partial, or no recovery of kidney function at 1 year between patients treated with immunosuppression and those not treated with immunosuppression (29% vs. 36%, 30.8% vs. 20.5% and 40.4 % vs. 43.6%, respectively). Kidney survival at 1, 3, and 5 years was similar among treated and untreated patients (85% vs. 81%, 77% vs. 76% and 72% vs. 66%, respectively). Despite the PSM analysis, no significant differences were observed in kidney survival between the two groups. Fourteen patients (27%) treated with immunosuppression had serious adverse events. Conclusions: Immunosuppressive treatments do not modify the unfavorable prognosis of patients with IgAN who are aged ≥50 years presenting with AKI-MH, and are frequently associated with severe complications.

Late thrombotic complications after SARS-CoV-2 infection in hemodialysis patients.

INTRODUCTION: There is an increased risk of thrombotic complications in patients with COVID-19. Hemodialysis patients are already at an increased risk for thromboembolic events such as stroke and pulmonary embolism. The aim of our study was to determine the incidence of late thrombotic complications (deep vein thrombosis, pulmonary embolism, stroke, new-onset vascular access thrombosis) in maintenance hemodialysis patients after recovery from COVID-19. METHODS: We performed a retrospective cohort study of 200 prevalent hemodialysis patients in our center at the start of the pandemic. We excluded incident patients after the cohort entry date and those who required hemodialysis for acute kidney injury, and excluded patients with less than 1 month follow-up due to kidney transplantation or death from non-thrombotic causes. FINDINGS: One-hundred and eighty five prevalent hemodialysis patients finally met the inclusion criteria; 37 patients (17.6%) had SARS-CoV-2 infection, out of which 10 (27%) died during the acute phase of disease without evidence of thrombotic events. There was an increased risk of thrombotic events in COVID-19 survivors compared to the non-infected cohort (18.5% vs. 1.9%, p = 0.002) after a median follow-up of 7 months. Multivariate regression analysis showed that COVID-19 infection increased risk for late thrombotic events adjusted for age, sex, hypertension, diabetes, antithrombotic treatment, and previous thrombotic events (Odds Ratio (OR) 26.4, 95% confidence interval 2.5-280.6, p = 0.01). Clinical and laboratory markers did not predict thrombotic events. CONCLUSIONS: There is an increased risk of late thrombotic complications in hemodialysis patients after infection with COVID-19. Further studies should evaluate the benefit of prolonged prophylactic anticoagulation in hemodialysis patients after recovery from COVID-19.

Risk factors for non-diabetic renal disease in diabetic patients.

BACKGROUND: Diabetic patients with kidney disease have a high prevalence of non-diabetic renal disease (NDRD). Renal and patient survival regarding the diagnosis of diabetic nephropathy (DN) or NDRD have not been widely studied. The aim of our study is to evaluate the prevalence of NDRD in patients with diabetes and to determine the capacity of clinical and analytical data in the prediction of NDRD. In addition, we will study renal and patient prognosis according to the renal biopsy findings in patients with diabetes. METHODS: Retrospective multicentre observational study of renal biopsies performed in patients with diabetes from 2002 to 2014. RESULTS: In total, 832 patients were included: 621 men (74.6%), mean age of 61.7 ± 12.8 years, creatinine was 2.8 ± 2.2 mg/dL and proteinuria 2.7 (interquartile range: 1.2-5.4) g/24 h. About 39.5% (n = 329) of patients had DN, 49.6% (n = 413) NDRD and 10.8% (n = 90) mixed forms. The most frequent NDRD was nephroangiosclerosis (NAS) (n = 87, 9.3%). In the multivariate logistic regression analysis, older age [odds ratio (OR) = 1.03, 95% CI: 1.02-1.05, P < 0.001], microhaematuria (OR = 1.51, 95% CI: 1.03-2.21, P = 0.033) and absence of diabetic retinopathy (DR) (OR = 0.28, 95% CI: 0.19-0.42, P < 0.001) were independently associated with NDRD. Kaplan-Meier analysis showed that patients with DN or mixed forms presented worse renal prognosis than NDRD (P < 0.001) and higher mortality (P = 0.029). In multivariate Cox analyses, older age (P < 0.001), higher serum creatinine (P < 0.001), higher proteinuria (P < 0.001), DR (P = 0.007) and DN (P < 0.001) were independent risk factors for renal replacement therapy. In addition, older age (P < 0.001), peripheral vascular disease (P = 0.002), higher creatinine (P = 0.01) and DN (P = 0.015) were independent risk factors for mortality. CONCLUSIONS: The most frequent cause of NDRD is NAS. Elderly patients with microhaematuria and the absence of DR are the ones at risk for NDRD. Patients with DN presented worse renal prognosis and higher mortality than those with NDRD. These results suggest that in some patients with diabetes, kidney biopsy may be useful for an accurate renal diagnosis and subsequently treatment and prognosis.

IgA Nephropathy in Elderly Patients.

BACKGROUND AND OBJECTIVES: Some studies suggest that the incidence of IgA nephropathy is increasing in older adults, but there is a lack of information about the epidemiology and behavior of the disease in that age group. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective multicentric study, we analyzed the incidence, forms of presentation, clinical and histologic characteristics, treatments received, and outcomes in a cohort of 151 patients ≥65 years old with biopsy-proven IgA nephropathy diagnosed between 1990 and 2015. The main outcome was a composite end point of kidney replacement therapy or death before kidney replacement therapy. RESULTS: We found a significant increase in the diagnosis of IgA nephropathy over time from six patients in 1990-1995 to 62 in 2011-2015 (P value for trend =0.03). After asymptomatic urinary abnormalities (84 patients; 55%), AKI was the most common form of presentation (61 patients; 40%). Within the latter, 53 (86%) patients presented with hematuria-related AKI (gross hematuria and tubular necrosis associated with erythrocyte casts as the most important lesions in kidney biopsy), and eight patients presented with crescentic IgA nephropathy. Six (4%) patients presented with nephrotic syndrome. Among hematuria-related AKI, 18 (34%) patients were receiving oral anticoagulants, and this proportion rose to 42% among the 34 patients older than 72 years old who presented with hematuria-related AKI. For the whole cohort, survival rates without the composite end point were 74%, 48%, and 26% at 1, 2, and 5 years, respectively. Age, serum creatinine at presentation, and the degree of interstitial fibrosis in kidney biopsy were risk factors significantly associated with the outcome, whereas treatment with renin-angiotensin-aldosterone blockers was associated with a lower risk. Immunosuppressive treatments were not significantly associated with the outcome. CONCLUSIONS: The diagnosis of IgA nephropathy among older adults in Spain has progressively increased in recent years, and anticoagulant therapy may be partially responsible for this trend. Prognosis was poor. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_07_16_CJASNPodcast_19_08_.mp3.

Diabetic Nephropathy without Diabetes.

Diabetic nephropathy without diabetes (DNND), previously known as idiopathic nodular glomerulosclerosis, is an uncommon entity and thus rarely suspected; diagnosis is histological once diabetes is discarded. In this study we describe two new cases of DNND and review the literature. We analyzed all the individualized data of previous publications except one series of attached data. DNND appears to be favored by recognized cardiovascular risk factors. However, in contrast with diabetes, apparently no factor alone has been demonstrated to be sufficient to develop DNND. Other factors not considered as genetic and environmental factors could play a role or interact. The most plausible hypothesis for the occurrence of DNND would be a special form of atherosclerotic or metabolic glomerulopathy than can occur with or without diabetes. The clinical spectrum of cardiovascular risk factors and histological findings support this theory, with hypertension as one of the characteristic clinical features.

Effectiveness of mycophenolate mofetil in C3 glomerulonephritis.

C3 glomerulonephritis is a clinicopathologic entity defined by the presence of isolated or dominant deposits of C3 on immunofluorescence. To explore the effect of immunosuppression on C3 glomerulonephritis, we studied a series of 60 patients in whom a complete registry of treatments was available over a median follow-up of 47 months. Twenty patients had not received immunosuppressive treatments. In the remaining 40 patients, 22 had been treated with corticosteroids plus mycophenolate mofetil while 18 were treated with other immunosuppressive regimens (corticosteroids alone or corticosteroids plus cyclophosphamide). The number of patients developing end-stage renal disease was significantly lower among treated compared with untreated patients (3 vs. 7 patients, respectively). No patient in the corticosteroids plus mycophenolate mofetil group doubled serum creatinine nor developed end-stage renal disease, as compared with 7 (significant) and 3 (not significant), respectively, in patients treated with other immunosuppressive regimens. Renal survival (100, 80, and 72% at 5 years) and the number of patients achieving clinical remission (86, 50, and 25%) were significantly higher in patients treated with corticosteroids plus mycophenolate mofetil as compared with patients treated with other immunosuppressive regimens and untreated patients, respectively. Thus, immunosuppressive treatments, particularly corticosteroids plus mycophenolate mofetil, can be beneficial in C3 glomerulonephritis.

Silent diabetic nephropathy.

AIM: To examine the risk of renal events in patients with biopsy-proven diabetic nephropathy (DN) and its possible associated factors. METHODS: Clinical and histological data of 60 patients diagnosed with diabetic nephropathy were retrospectively collected. Patients with evidence or suspicion of other nephropathies were excluded from the study. The final event was defined as renal replacement therapy (RRT) initiation or progression of chronic kidney disease (CKD), according to the KDIGO 2012 definition of a decrease in CKD category and a decrease in GFR of 25% or more. RESULTS: A total of 45 patients with a follow-up of at least 3 mo were included. Most of the patients presented type 2 DM, with a mean age of 58.3 years old. The time of evolution of DM was 9.6 ± 7.8 years, although in 13 patients, it was less than 5 years. A total of 62% of patients reached the final event in a median period of 3.4 years (95%CI: 2.1-4.7), with 21 of them requiring dialysis. The factors that were independently associated with renal survival were estimated glomerular filtration rate (eGFR) at the time of biopsy, cardiovascular disease (CVD) history and HbA1c less than 7%. Therefore, for each 10 mL/min per 1.73 m(2) reduction in eGFR, we obtained a DN progression risk of HR = 2 (1.3-3.0) (P = 0.001); patients with CVD were at greater risk for DN progression (HR = 2.8, 1.1-7.1, P = 0.032), and CKD patients with HbA1c < 7% demonstrated greater renal risk than patients with HbA1c ≥ 7%, with an HR of 2.9 (1.0-8.4) (P = 0.054). CONCLUSION: A past history of CVD is a risk factor for DN progression. Levels of HbA1c less than 7% could favor an eGFR decrease in these patients.

Perceived health-related quality of life and comorbidity in diabetic patients starting dialysis (CALVIDIA study).

BACKGROUND: Diabetes mellitus (DM) is a widespread prevalent illness, currently the main cause of end-stage renal disease (ESRD). MATERIAL AND METHODS: In a longitudinal, prospective study we compared two cohorts of patients starting dialysis therapy, diabetic and non-diabetic ESRD patients. Perceived health was measured by the Medical Outcomes Study Short-Form 36 (SF-36) questionnaire, functional status by the Karnofsky scale and comorbidity by the Charlson age-comorbidity index. A broad spectrum of variables in relation to diabetes, ESRD, comorbidity and renal replacement therapy (RRT) were studied, as well as the distribution of comorbidity frequencies at dialysis start. RESULTS: Thirty-four Spanish centers included 232 diabetic patients, 43 type 1 and 189 type 2, mean diabetes duration 18 +/- 9 yrs, and five centers included 121 non-diabetic patients. Out of the 232 diabetic patients, 187 patients (81%) started hemodialysis (HD) and 45 patients (19%) started peritoneal dialysis (PD) (vs. 82% and 18%, respectively in non-diabetic patients). Transient vascular access (VA) for starting RRT was required in 54% of the diabetic patients vs. 53% in the nondiabetic patients. When both study groups were compared, diabetic patients required antihypertensive drugs more frequently than non-diabetic patients and showed higher systolic blood pressure (BP), as well as higher cardiovascular (CV) complication incidences, poorer SF-36 physical component summary scores and mental component summary scores and worse Karnofsky scale scores, with the Charlson age-comorbidity score being higher. CONCLUSION: Diabetic patients starting dialysis in Spain are more often type 2 diabetics, have worse perceived health-related quality of life (HRQoL) in relation to non-diabetic patients, worse functional status and higher incidences of prognostic mortality markers.

Perceived mental health at the start of dialysis as a predictor of morbidity and mortality in patients with end-stage renal disease (CALVIDIA Study).

BACKGROUND: Health-related quality of life may affect morbidity and survival in end-stage renal disease, but it is not clear whether coexisting comorbidity and other known prognostic variables could account for such an association. METHODS: To study the relationship between health-related quality of life and morbidity and survival, we carried out an inception cohort study in patients starting chronic dialysis, mostly diabetics, with a follow-up of 1-3 years in 34 Spanish hospitals. Health-related quality of life was measured by the SF-36 Health Survey and Karnofsky scale. Charlson age-comorbidity index and other prognostic clinical variables were measured concurrently. The primary outcome variable was time until death and the secondary outcome was hospitalization days. RESULTS: Of 318 patients enrolled (208 diabetics), with a median follow-up of 771 days, 80 died. In the unadjusted analysis, all-cause mortality was associated with lower SF-36 physical and mental component scores and Karnofsky scale. In the adjusted analysis, SF-36 mental component score predicted all-cause mortality (hazard ratio for a 10 point decrease: 1.28; 95% confidence interval: 1.05-1.56). The SF-36 mental component score also predicted more hospitalization days (adjusted risk ratio of each additional hospital day associated with every 10 point decrease: 1.25; 95% confidence interval: 1.08-1.45). Among diabetics, both the SF-36 physical and mental components predicted mortality and hospitalization days. CONCLUSIONS: In end-stage renal disease, perceived mental health is an independent predictor of mortality and morbidity, mainly among diabetics patients.