Qian, Qi

Summary at a GlanceAs the population ages, large numbers of elderly patients will present with kidney diseases. Kidney biopsy for elderly patients is generally well tolerated and informative. Compared with younger adults, IgA nephropathy in the elderly carries a poor prognosis. In patients with intercurrent infections, IgA‐dominant postinfectious GN should be carefully differentiated from idiopathic IgA nephropathy. Existing ESRD and mortality prediction models/scoring systems for IgA nephropathy may not be generalized to elderly patients.

AbstractAcid‐base alterations in patients with kidney failure and on hemodialysis (HD) treatment contribute to (1) intradialytic hypercapnia and hypoxia, (2) hemodynamic instability and cardiac arrhythmia, (3) systemic inflammation, and (4) a number of associated electrolyte alterations including potentiating effects of hypokalemia, hypocalcemia and, chronically, soft‐tissue and vascular calcification, imparting poor prognosis and mortality. This paper discusses acid‐base regulation and pathogenesis of dysregulation in patients with kidney failure. Major organ and systemic effects of acid‐base perturbations with a specific focus on kidney failure patients on HD are emphasized, and potential mitigating strategies proposed. The high rate of HD‐related complications, specifically those that can be accounted for by rapid and steep acid‐base perturbations imposed by HD treatment, attests to the pressing need for investigations to establish a better dialysis regimen.

For decades, lactic acid has been considered a dead-end product of glycolysis. Research in the last 20+ years has shown otherwise. Through its transporters (MCTs) and receptor (GPR81), lactic acid plays a key role in multiple cellular processes, including energy regulation, immune tolerance, memory formation, wound healing, ischemic tissue injury, and cancer growth and metastasis. We summarize key findings of lactic acid signaling, functions, and many remaining questions.

Serum response factor (SRF) was found to be involved in the phenotypic transition and fibrosis of the peritoneal membrane during treatment with peritoneal dialysis (PD), but the exact mechanism remains unclear. SRF regulates microRNAs (miRNAs) that contain the SRF-binding consensus (CArG) element in the promoter region. Therefore, we investigated whether the miR-199a/214 gene cluster, which contains a CArG element in its promoter, is directly regulated by SRF. High-glucose (HG) treatment significantly unregulated the expression of the miR-199a-5p/214–3p gene cluster in human peritoneal mesothelial cells (HPMCs). By chromatin immunoprecipitation and reporter assays, we found that SRF binds to the miR-199a-5p/214–3p gene cluster promoter after HG stimulation. In vitro , in HPMCs, silencing of miR-199a-5p or miR-214–3p inhibited the HG-induced phenotypic transition and cell migration but enhanced cell adhesion, whereas ectopic expression of mimic oligonucleotides had the opposite effects. Both miR-199a-5p and miR-214–3p targeted claudin-2 and E-cadherin mRNAs. In a PD rat model, treatment with an SRF inhibitor silenced miR-199a-5p and miR-214–3p and alleviated HG-PD fluid–induced damage and fibrosis. Overall, this study reveals a novel SRF–miR-199a/miR-214–E-cadherin/claudin-2 axis that mediates damage and fibrosis in PD.

Elevated protein catabolism and protein malnutrition are common in patients with chronic kidney disease (CKD) and end‐stage renal disease (ESRD). The underlying etiology includes, but is not limited to, metabolic acidosis intestinal dysbiosis; systemic inflammation with activation of complements, endothelin‐1 and renin‐angiotensin‐aldosterone (RAAS) axis; anabolic hormone resistance; energy expenditure elevation; and uremic toxin accumulation. All of these derangements can further worsen kidney function, leading to poor patient outcomes. Many of these CKD‐related derangements can be prevented and substantially reversed, representing an area of great potential to improve CKD and ESRD care. This review integrates known information and recent advances in the area of protein nutrition and malnutrition in CKD and ESRD. Management recommendations are summarized. Thorough understanding the pathogenesis and etiology of protein malnutrition in CKD and ESRD patients will undoubtedly facilitate the design and development of more effective strategies to optimize protein nutrition and improve outcomes.

Abstract Renal fibrosis is the common pathological hallmark of progressive chronic kidney disease ( CKD ) with diverse aetiologies. Recent researches have highlighted the critical role of hypoxia during the development of renal fibrosis as a final common pathway in end‐stage kidney disease ( ESKD ), which joints the scientist's attention recently to exploit the molecular mechanism underlying hypoxia‐induced renal fibrogenesis. The scaring formation is a multilayered cellular response and involves the regulation of multiple hypoxia‐inducible signalling pathways and complex interactive networks. Therefore, this review will focus on the signalling pathways involved in hypoxia‐induced pathogenesis of interstitial fibrosis, including pathways mediated by HIF , TGF ‐β, Notch, PKC / ERK , PI 3K/Akt, NF ‐κB, Ang II / ROS and micro RNA s. Roles of molecules such as IL ‐6, IL ‐18, KIM ‐1 and ADO are also reviewed. A comprehensive understanding of the roles that these hypoxia‐responsive signalling pathways and molecules play in the context of renal fibrosis will provide a foundation towards revealing the underlying mechanisms of progression of CKD and identifying novel therapeutic targets. In the future, promising new effective therapy against hypoxic effects may be successfully translated into the clinic to alleviate renal fibrosis and inhibit the progression of CKD .

Both vitamin D deficiency and cognitive impairment are common in patients with chronic kidney disease (CKD). Vitamin D exerts neuroprotective and regulatory roles in the central nervous system. Hypovitaminosis D has been associated with muscle weakness and bone loss, cardiovascular diseases (hypertension, diabetes and hyperlipidemia), inflammation, oxidative stress, immune suppression and neurocognitive impairment. The combination of hypovitaminosis D and CKD can be even more debilitating, as cognitive impairment can develop and progress through vitamin D-associated and CKD-dependent/independent processes, leading to significant morbidity and mortality. Although an increasingly recognized comorbidity in CKD, cognitive impairment remains underdiagnosed and often undermanaged. Given the association of cognitive decline and hypovitaminosis D and their deleterious effects in CKD patients, determination of vitamin D status and when appropriate, supplementation, in conjunction with neuropsychological screening, should be considered integral to the clinical care of the CKD population.

Background. The study investigates the occurrence, severity, and outcomes of acute kidney injury (AKI) in octogenarians following heart valve surgery.Methods. All patients, age>80 years, not on dialysis and without kidney transplant, undergoing heart valve replacement at Mayo Clinic, Rochester, in the years 2002-2003 were enrolled. AKI was diagnosed based on AKIN criteria.Results. 209 octogenarians (88.0% aortic valve, 6.2% mitral valve, 1.0% tricuspid valve, and 4.8% multivalve) with (58.4%) and without CABG were studied. 34 (16.3%) had preexisting CKD. After surgery, 98 (46.8%) developed AKI. 76.5% of the AKI were in Stage 1, 9.2% in Stage 2, and 14.3% in Stage 3. 76.5% CKD patients developed AKI. Length of hospital stay was longer for AKI patients. More AKI patients were discharged to care facilities. Patient survival at 30 days and 1 year for AKI versus non-AKI was 88.8 versus 98.7%,p=0.003, and 76.5 versus 88.3%,p=0.025, respectively. With follow-up of3.94±0.28years, Kaplan-Meier analysis showed a reduced survival for AKI octogenarians. Preexisting CKD and large volume intraoperative fluid administration were independent AKI predictors.Conclusions. Nearly half of the octogenarians developed AKI after valve replacement surgery. AKI was associated with significant functional impairment and reduced survival.

AbstractAimData on clinicopathological features, treatment and outcomes of IgA nephropathy (IgAN) in elderly patients are limited.MethodsNative kidney biopsies with a pathological diagnosis of IgAN (n = 1084) from Mayo Clinic Rochester in the years 1994–2013 were examined. After exclusion of the secondary IgAN, 45 elderly IgAN patients (age ≥65 years) were identified. One hundred sixty‐two younger adults (age 18–64 years) with IgAN were randomly selected for comparison.ResultsCompared with younger adults, elderly patients showed a higher rate of chronic hypertension (62.2 vs 27.2%), higher pulse pressures (65 ± 17 vs 51 ± 15 mmHg), requiring greater number of antihypertensive medications (2.5 ± 1.2 vs 1.7 ± 0.7) and lower blood haemoglobin (11.1 ± 2.3 vs 12.7 ± 2.1 g/dL) at time of kidney biopsy, all P < 0.001. Pathologically, elderly kidneys showed a higher degree of tubulointerstitial fibrosis (P = 0.04) and vascular sclerosis (P < 0.001). Treatments (including the use of angiotensin‐converting enzyme inhibitor (ACEI) inhibitor, angiotensin II receptor blocker (ARB) and immunosuppressants) were similar in the two cohorts. Elderly patients had more end‐stage renal disease at 6 months (HR 5.51; 95% CI 1.46–22.3, P = 0.01) and higher 6‐month and 5‐year mortality (HR 2.31; 95% CI 1.04–5.17, P = 0.04) after adjusting the age and comorbidities.ConclusionIgAN diagnosed at age >65 years tends to have a faster renal disease progression and higher patient mortality.