Worsening azotemia in older susceptible CKD patients on AB, often but not always associated with known precipitating risk factors, remains under-recognized. Sustained improved eGFR often follows the discontinuation of AB. The practising physician should be well aware of these syndromes. Our observations call for further study.

The ACEI, captopril was introduced into clinical medicine in the early 1970s for hypertension. Other ACEIs and the ARBs were introduced subsequently. Following several RAAS blockade trials, we now have an expanded set of clinical indications for these agents. Despite the escalated use of these agents, we continue to experience an unexplained epidemic of ESRD/CKD/ARF. There are concerns regarding potential iatrogenic renal failure arising from these agents. A case, it would appear, of unintended consequences. Our publication of several reports on the previously unrecognized syndrome of late onset renal failure from angiotensin blockade (LORFFAB) in 2008 adds to this evolving literature. At the same time, some recent reports have questioned the veracity of claims of superior reno-protection with these agents beyond BP lowering. A post hoc analysis of a subset of patients in the MICRO-HOPE cohort suggested that a previously unrecognized greater 24-h BP lowering achieved in the ramipril arm vs placebo could explain the reported benefits of the ACEI. These doubts and concerns became heightened by the results of the ONTARGET study. Our critical re-appraisal of the large RAAS blockade trials revealed design flaws and protocol contradictions that further these doubts and concerns. We conclude that these agents be used more judiciously, with better monitoring of kidney function. Treating physicians must consider drug discontinuation in selected patients. We also support temporary withdrawal of these agents before major surgical procedures, contrast media administration and during acute illness. Such preventative measures (reno-prevention) would enhance the benefits of reno-protection with RAAS blockade.

By most estimates, we have an increasing worldwide end-stage renal disease (ESRD) epidemic. This is despite at least two decades of intensified reno-protection strategies, including attempts at optimal hypertension management, optimization of diabetic control, smoking cessation efforts, and the extensive application of renin-angiotensin-aldosterone system (RAAS) blockade in both diabetic and nondiabetic chronic nephropathies. The current consensus is that chronic kidney disease (CKD) progression to ESRD is a continuous, progressive, and predictable loss of estimated glomerular filtration rate (eGFR) in CKD patients, inexorably leading to ESRD. Our recent experience in a Mayo Health System Hypertension Clinic, as well as new reports associating ESRD development in CKD patients with episodes of acute kidney injury (AKI), led us to hypothesize that CKD to ESRD progression may not be that predictable, after all. Among a 100 high-risk CKD patient cohort that we have followed up prospectively since 2002, we demonstrated that in 15 of 17 (88%) patients who progressed to ESRD, progression from CKD to ESRD was unpredictable, nonlinear, abrupt, and rapid, and this followed AKI secondary to medical and surgical events. We have coined a new term, the syndrome of rapid-onset end-stage renal disease (SORO-ESRD), to represent this unrecognized syndrome. Larger studies are warranted to confirm our single-center findings. If confirmed to represent a significant proportion of the ESRD population, at least here in the United States, this finding will demand major paradigm shifts in the current concepts of reno-protection and "A-V Fistula first" programs.

Hyperkalemia is an electrolyte abnormality with potentially life-threatening consequences. Despite various guidelines, no universally accepted consensus exists on best practices for hyperkalemia monitoring, with variations in precise potassium (K þ) concentration thresholds or for the management of acute or chronic hyperkalemia. Based on the available evidence, this review identifies several critical issues and unmet needs with regard to the management of hyperkalemia. Real-world studies are needed for a better understanding of the prevalence of hyperkalemia outside the clinical trial setting. There is a need to improve effective management of hyperkalemia, including classification and K þ monitoring, when to reinitiate previously discontinued renin-angiotensin-aldosterone system inhibitor (RAASi) therapy, and when to use oral K þ-binding agents. Monitoring serum K þ should be individualized; however, increased frequency of monitoring should be considered for patients with chronic kidney disease, diabetes, heart failure, or a history of hyperkalemia and for those receiving RAASi therapy. Recent clinical studies suggest that the newer K þ binders (patiromer sorbitex calcium and sodium zirconium cyclosilicate) may facilitate optimization of RAASi therapy. Enhancing the knowledge of primary care physicians and internists with respect to the safety profiles of these newer K þ binders may increase confidence in managing patients with hyperkalemia. Lastly, the availability of newer K þ-binding agents requires further study to establish whether stringent dietary K þ restrictions are needed in patients receiving K þ-binder therapy. Individualized monitoring of serum K þ among patients with an increased risk of hyperkalemia and the use of newer K þ-binding agents may allow for optimization of RAASi therapy and more effective management of hyperkalemia.

Background: Continental Africa is facing an epidemic of chronic kidney disease (CKD). APOL1 risk variants have been shown to be strongly associated with an increased risk for non-diabetic kidney disease including HIV nephropathy, primary non-monogenic focal and segmental glomerulosclerosis, and hypertension-attributed nephropathy among African ancestry populations in the USA. The world's highest frequencies of APOL1 risk alleles have been reported in West African nations, overlapping regions with a high incidence of CKD and hypertension. One such region is south-eastern Nigeria, and therefore we sought to quantify the association of APOL1 risk alleles with CKD in this region. Methods: APOL1 risk variants were genotyped in a case-control sample set consisting of non-diabetic, CKD patients (n = 44) and control individuals (n = 43) from Enugu and Abakaliki, Nigeria. Results: We found a high frequency of two APOL1 risk alleles in the general population of Igbo people of south-eastern Nigeria (23.3%). The two APOL1 risk allele frequency in the CKD patient group was 66%. Logistic regression analysis under a recessive inheritance model showed a strong and significant association of APOL1 two-risk alleles with CKD, yielding an odds ratio of 6.4 (unadjusted p = 1.2E-4); following correction for age, gender, HIV and BMI, the odds ratio was 4.8 (adjusted p = 5.1E-03). Conclusion: APOL1 risk variants are common in the Igbo population of south-eastern Nigeria, and are also highly associated with non-diabetic CKD in this area. APOL1 may explain the increased prevalence of CKD in this region.

Current epidemiological data from the USA, Europe, Asia and the Indian subcontinent, Africa, the Far East, South America, the Middle East and Eastern Europe all point to the increasing incidence of renal failure encompassing acute kidney injury (AKI), chronic kidney disease (CKD) and end-stage renal disease (ESRD). While the explanations for these worldwide epidemics remain speculative, it must be acknowledged that these increases in AKI, CKD and ESRD, happening worldwide, have occurred despite the universal application of strategies of renoprotection over the last 2 decades, more especially the widespread use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). We note that many of the published large renin-angiotensin-aldosterone system (RAAS) blockade randomized controlled trials, upon which current evidence-based practice for the increasing use of ACEIs and ARBs for renoprotection derived from, have strong deficiencies that have been highlighted over the years. From reports in the literature, there is an increasing association of exacerbations of renal failure with ACEIs and ARBs, more so in the older hypertensive patient, >65 years old. The biological plausibility for ACEI and ARB to protect the kidneys against a background of potential multiple pathogenetic pathways to account for CKD progression appears to be not very defensible. We reviewed the literature along these lines and submit that ACEIs and ARBs often cause unrecognized significant worsening renal failure in CKD patients, sometimes irreversible, and that more caution is required regarding their use, especially in the older hypertensive patients, with likely ischemic hypertensive nephropathy. Given the increasing association of concomitant RAAS blockade with worsening renal failure following exposure to iodinated contrast, during acute illness, in the perioperative period and following lower bowel preparations prior to colonoscopy, we submit that, preferably, ACEIs and ARBs be withheld for 2–4 days prior to or during these clinical scenarios. This represents the concept of renoprevention.

Background Cardiovascular disease among hemodialysis (HD) patients is linked to poor outcomes. The Acute Dialysis Quality Initiative Workgroup proposed echocardiographic (ECHO) criteria for structural heart disease (SHD) in dialysis patients. The association of SHD with patient-important outcomes is not well defined. Objectives We determined prevalence of ECHO determined SHD and its association with survival among incident HD patients. Methods We analyzed patients initiating chronic HD from 2001-2013 who underwent ECHO ≤ 1 month prior to or ≤ 3 months following HD initiation (n = 654). Results Mean patient age was 66 ± 16 years, and 60% of patients were male. ECHO findings that met 1 or more and ≥ 3 of the new criteria were discovered in 87% and 54% of patients, respectively. Over a median of 2.4 years, 415 patients died: 108 (26%) died within 6 months. Five-year mortality was 62%. Age- and gender-adjusted structural heart disease variables associated with death were left ventricular ejection fraction (LEVF) ≤ 45% (HR 1.48, CI 1.20-1.83) and right ventricular (RV) systolic dysfunction (HR 1.68, CI 1.35-2.07). An additive of higher death risk included LVEF ≤ 45% and RV systolic dysfunction rather than neither (HR 2.04, CI 1.57-2.67; p = 0.53 for test for interaction). Following adjustment for age, gender, race, diabetic kidney disease, and dialysis access, RV dysfunction was independently associated with death (HR 1.66; CI 1.34-2.06; p < 0.001). Conclusions SHD was common in our hemodialysis study population, and RV systolic dysfunction independently predicted mortality.

on the kidney. In proteinuric rats, the combination of ACEi and a low sodium diet elicits pronounced renal interstitial damage, despite a significant reduction of proteinuria. 2 As similar effects were found in healthy rats, the renal damage was not owing to particularities of the model, but related to the ACEi regimen. This is in line with earlier data in experimental renal transplantation, with monotherapy ACEi. 3 These data are distressing, as the ACEi regimens induced renal fibrosis in spite of a reduction in proteinuria and blood pressure, that is, an improvement of the established clinical criteria for a good response to therapy. In human, it is usually not feasible to monitor renal structural damage during therapy. Accordingly, considering the dissociation between renal fibrosis and the intermediate parameters blood pressure and proteinuria, therapy-associated progressive renal damage during renin-angiotensin system blockade in human cannot easily be recognized, and would require large, hard end point studies to become manifest. Although the mechanism underlying the ACEiinduced renal fibrosis deserves further study, our data provide a possible explanation for the increased risk of end-stage renal disease found by Suissa et al. 1 The incidence of end-stage renal disease is increasing worldwide, despite extensive use of renin-angiotensin system blockers. It would be prudent not to take their long-term renoprotective effect for granted, scrutinize their effects on renal structural damage in experimental studies, and critically evaluate their outcome in human during long-term follow-up. 1. Suissa S, Hutchinson T, Brophy JM et al. ACE-inhibitor use and the long-term risk of renal failure in diabetes. Kidney Int 2006; 69: 913-919. 2. Hamming I, Navis G, Kocks M et al. ACE inhibition has adverse renal effects during dietary sodium restriction in proteinuric and healthy rats.