Case Study: The Weighty Issue of Treatment Options for Obese Dialysis Patients.

Obesity is a complex chronic disease and common comorbidity in kidney failure and is the leading causes of death and disability in this population. Guidelines do not specifically address the preferred weight management option(s) for obesity while on dialysis. Large body size is a limiting factor for consideration of a kidney transplantation. We report on a successful bariatric surgery with a young adult after 5.5 years on dialysis with hope for a future transplant. Success was demonstrated with progressive weight loss without adverse changes in renal clinical markers accompanied by improvements in exercise tolerance and health status thereby improving her suitability for a kidney transplant. Further studies and guidelines are needed to address weight loss options for those with obesity on dialysis and want to lose weight.

Syndrome of rapid onset ESRD accounted for high hemodialysis catheter use--results of a 13-year Mayo Clinic incident hemodialysis study.

BACKGROUND: The syndrome of rapid onset end-stage renal disease (SORO-ESRD) was first described in the journal Renal Failure in 2010. This is an acute precipitate unpredictable yet irreversible ESRD following acute kidney injury (AKI), as distinct from "classic" ESRD where chronic kidney disease (CKD)-ESRD progression was linear, time-dependent, and predictable. The overall impact of SORO-ESRD on ESRD outcomes in the adult US ESRD population remains speculative and called for larger studies. METHODS: A retrospective investigation of an incident adult ESRD population, Mayo Clinic, Rochester, 2001-2013. RESULTS: One hundred and forty-nine of 1461 (10%) incident patients with ESRD had SORO-ESRD - M:F = 76:73, age 62 (19-95) years, 139 (93%) native kidneys, and 10 (7%) renal transplant recipients (RTRs). The modal age group was 71-80 years. A total of 147 (99%) SORO-ESRD patients started first hemodialysis treatment via a dialysis catheter. Kidney biopsy in 10 RTRs and 34 native kidneys revealed acute tubular necrosis (ATN) as the commonest pathology. Cardiac arrest remained the leading cause of death among SORO-ESRD patients. CONCLUSIONS: SORO-ESRD accounted for 149 (10%) of 1461 incident ESRD patients. There was no gender disparity. The older population was more susceptible. Ninety-nine percent (99%) of SORO-ESRD patients started their first hemodialysis treatment via a dialysis catheter, a major negative impact on AV fistula first programs. ATN was the leading pathologic diagnosis. We conclude that SORO-ESRD contributes significantly to incident ESRD here in the USA including renal allograft loss. Efforts to reduce AKI incidence or renoprevention demand more attention and priority.

Unexplained hypotension and exertional dyspnea in a night-cycled peritoneal dialysis patient--a rare form of icodextrin hypersensitivity.

In recent years, icodextrin 7.5% has been used in PD as an alternative to glucose to achieve sustained reliable ultrafiltration (UF) and clearance without adversely increasing glucose absorption. Icodextrin is generally well tolerated. The most commonly reported adverse events are cutaneous reactions. We report a rare form of hypersensitivity to icodextrin 7.5% that was accompanied by dyspnea and symptomatic hypotension, without increased UF to account for the observed hypotension. Icodextrin produces symptomatic hypotension in up to 40% of patients by a known mechanism of increased UF and corresponding weight loss. However, it can also produce symptomatic hypotension accompanied by several other systemic symptoms in a hypersensitivity reaction. Discontinuation of the icodextrin results in prompt resolution of those symptoms. Treating nephrologists must be aware of this rare form of icodextrin hypersensitivity.

High population frequencies of APOL1 risk variants are associated with increased prevalence of non-diabetic chronic kidney disease in the Igbo people from south-eastern Nigeria.

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.

The CKD enigma with misleading statistics and myths about CKD, and conflicting ESRD and death rates in the literature: results of a 2008 U.S. population-based cross-sectional CKD outcomes analysis.

The just released (August 2012) U.S. Preventive Services Task Force (USPSTF) report on chronic kidney disease (CKD) screening concluded that we know surprisingly little about whether screening adults with no signs or symptoms of CKD will improve health outcomes and that clinicians and patients deserve better information on CKD. The implications of the recently introduced CKD staging paradigm versus long-term renal outcomes remain uncertain. Furthermore, the natural history of CKD remains unclear. We completed a comparison of US population-wide CKD to projected annual incidence of end stage renal disease (ESRD) for 2008 based on current evidence in the literature . Projections for new ESRD resulted in an estimated 840,000 new ESRD cases in 2008, whereas the actual reported new ESRD incidence in 2008, according to the 2010 USRDS Annual Data Report, was in fact only 112,476, a gross overestimation by about 650%. We conclude that we as nephrologists in particular, and physicians in general, still do not understand the true natural history of CKD. We further discussed the limitations of current National Kidney Foundation Disease Outcomes Quality Initiative (NKF KDOQI) CKD staging paradigms. Moreover, we have raised questions regarding the CKD patients who need to be seen by nephrologists, and have further highlighted the limitations and intricacies of the individual patient prognostication among CKD populations when followed overtime, and the implications of these in relation to future planning of CKD care in general. Finally, the clear heterogeneity of the so-called CKD patient is brought into prominence as we review the very misleading concept of classifying and prognosticating all CKD patients as one homogenous patient population.

Evidence of the syndrome of rapid onset end-stage renal disease (SORO-ESRD) in the acute kidney injury (AKI) literature--preventable causes of AKI and SORO-ESRD--a call for re-engineering of nephrology practice paradigms.

INTRODUCTION: We described the previously unrecognized syndrome of rapid-onset end-stage renal disease (SORO-ESRD) in 2010, in the journal Renal Failure, as distinct from the classic CKD-ESRD progression of a methodical, linear, time-dependent and predictable progression from CKD through CKD stages I-V, ending in ESRD requiring renal replacement therapy (RRT). It remains unclear to what extent this syndrome may have been identified in the past without acknowledging its uniqueness. METHODS: We reviewed AKI reports and ascertained cases of SORO-ESRD as defined by patients with a priori stable kidney function who subsequently exhibited unanticipated and irreversible ESRD requiring RRT following new AKI episodes. RESULTS: Fifteen AKI reports demonstrating SORO-ESRD were analyzed. The reports span most regions of the world. The 15 studies with 20 to 1095 AKI patients each, mean age 39-65 years, published between 1975 and 2010, demonstrated SORO-ESRD rates from 1% to 85% of the AKI series. AKI was caused by hypovolemia/hypotension, infections/sepsis and exposure to nephrotoxics especially radiocontrast, NSAIDs, aminoglycosides and RAAS blocking agents, ACEIs and ARBs. DISCUSSION: Irreversible ESRD following AKI, consistent with our recent description of a new and unrecognized syndrome has been sporadically reported in the AKI literature, without a clear mandate as a syndrome, potentially distinct from the classic ESRD. The contribution of SORO-ESRD to the global ESRD pandemic, the impact of SORO-ESRD on AV-Fistula planning, any differential behavior of SORO-ESRD versus classic ESRD in terms of mortality outcomes and any predisposing factors to SORO-ESRD as advanced age and nephrotoxic exposure all call for serious research study.

Renoprevention: A new concept for reengineering nephrology care--an economic impact and patient outcome analysis of two hypothetical patient management paradigms in the CCU.

BACKGROUND: The impact of acute kidney injury (AKI) on chronic kidney disease (CKD) progression remains uncertain; the common belief is that AKI in CKD is short-lived with subsequent full recovery. However 25.2% of end-stage renal disease (ESRD) Medicare patients all experienced antecedent AKI. We recently described a new syndrome of ESRD following AKI, the syndrome of rapid-onset end-stage renal disease (SORO-ESRD). Renoprevention, which we described in 2009, is the application of preventative measures to reduce AKI incidence. METHODS: This is a descriptive study based on real clinical experience. Two hypothetical 69-year-old Caucasian male patients, A and B, with symptomatic coronary artery disease (CAD) presented for elective cardiac catheterization and subsequent coronary artery bypass graft procedures; renoprevention was applied in patient A but not in B. RESULTS: Aggressive fluid repletion, withholding Lisinopril 40 mg once daily (QD) 1 week before hospitalization (hydralazine substituted) in A-earlier discharge after 6 days, transient minimal change in serum creatinine. Patient B continued on Lisinopril 40 mg QD, experienced prolonged hypotension needing pressors-severe oliguric AKI, volume overload, daily RRT for 6 days, recovered kidney function, was discharged after 20 days. Hospital charges were $68,580 (A) versus $154,650 (B). If patient B had developed ESRD (SORO-ESRD), the savings would be humongous. CONCLUSION: A more forceful and pragmatic application of renoprevention strategies in the coronary care unit (CCU)-preemptive withholding of nephrotoxics including renin angiotensin aldosterone system (RAAS) blockers, aggressive prevention of perioperative hypotension, avoiding nephrotoxic exposure as contrast, and antibiotics-leads to less AKI, potentially less SORO-ESRD, better patient outcomes, and massive dollar savings. Such paradigm shifts would constitute major rethinking in current nephrology practice, a form of nephrology practice reengineering.

Nondialytic therapy for end-stage renal disease is an underutilized care paradigm in the United States: time for a more robust reappraisal of this treatment option.

Nondialytic therapy (NDT)--also calledconservative kidney management--is a growing modality of treatment for select chronic kidney disease and end-stage renal disease (ESRD) patients globally. Nevertheless, NDT is rarely practiced in the United States. We set out to investigate NDT activity before initiation of renal replacement therapy in a Northwestern Wisconsin Mayo Clinic ESRD population. Records of all prevalent ESRD patients on chronic hemodialysis in our practice were retrospectively reviewed in May 2012. Dialysis nurses and social workers were informally interviewed to augment the review process. Of the 166 ESRD patients reviewed, 82 (49%) were 70 years of age or older, 46 (28%) were 70-79 years, and 36 (22%) were 80-89 years. Most of these older patients had multiple significant comorbidities ("multimorbidity"). Evidence for NDT activity before initiation of renal replacement therapy was virtually nonexistent. The older ESRD patients with multimorbidity experienced frequent hospitalizations. Our preliminary review suggests that their quality of life may have been better with NDT. Almost one half of our ESRD population was made up of people more than 70 years of age, most with multimorbidity. In our practice, NDT is a neglected paradigm, as it is in most U.S. nephrology practices. The place of NDT, actively provided by a specialized multidisciplinary team, for U.S. ESRD patients demands urgent attention and robust reappraisal by U.S. nephrologists.

Renin-Angiotensin-Aldosterone System Blockade (RAASB) After Acute Kidney Injury: The Controversy Thickens on If and When to Discontinue RAASB.

Unquestionably, there is a common consensus regarding cardiorenal protection with renin-angiotensin-aldosterone system blockade (RAASB) in both diabetic and nondiabetic chronic kidney disease (CKD). Nevertheless, there remain conflicting retrospective reports regarding renal and cardiovascular mortality outcomes following discontinuation of RAASB in advanced CKD. We present an editorial on a recent article discussing renal and mortality outcomes among hospitalized veterans who were started back on RAASB versus those who were not started back on RAASB. The controversy surrounding this topic thickens as the analysis unfolds.

A Four-Year Report on Renal Outcomes Following the Elective Withdrawal of Long-Term Renin-Angiotensin-Aldosterone Blockade in a Cohort of Patients With Otherwise Inexplicable New-Onset and Progressive Acute Kidney Injury.

Background Renin-angiotensin-aldosterone (RAAS) blockade is acclaimed, by consensus, to be renoprotective in both diabetic and non-diabetic chronic kidney disease (CKD). Contradictory reports exist regarding renal and cardiovascular outcomes after stopping RAAS blockade in advanced CKD. A few prospective, non-randomized, cohort studies have demonstrated improvement in kidney function after discontinuation of RAAS blockade. In this study, we investigated renal and mortality outcomes following the elective withdrawal of RAAS blockade after otherwise inexplicable acute kidney injury (AKI). Methodology We conducted a retrospective cohort analysis of patients enrolled between February 2018 and May 2021. Kidney function was monitored after elective withdrawal of long-term RAAS blockade in CKD patients presenting with new-onset otherwise inexplicable progressive AKI, defined by a >25% increase in baseline serum creatinine. Results In total, 71 patients, 69 Caucasians, one African American, and one Hispanic, were included in the study, with a male-to-female ratio of 42:29, and a mean age of 69.4 (37-95) years. Through February 2022, 12 patients had died, with eight remaining on hemodialysis for end-stage renal disease. Of the remaining 51 patients followed for 706 (40-1,478) days, baseline serum creatinine was 1.30 ± 0.42 (0.66-2.70) mg/dL, peak enrollment serum creatinine was 2.17 ± 1.06 (1.1-8.3) mg/dL (n = 51, p < 0.0001, t = 6.4872, df = 135), and serum creatinine after four years was 1.58 ± 0.54 (0.84-3.3) mg/dL (n = 50, p < 0.0001, t = 5.1805, df = 119). Death in 11 of 12 (91%) patients was from non-renal causes, and most deaths occurred despite improved kidney function. Conclusions Our results demonstrate clearly improved renal outcomes in most patients following the elective withdrawal of long-term RAAS blockade in CKD patients with new-onset progressive yet otherwise inexplicable AKI without increased cardiovascular mortality.

Chronic Kidney Disease Burden in Low-Resource Settings: Regional Perspectives.

The burden of chronic kidney disease (CKD) has increased exponentially worldwide but more so in low- and middle-income countries. Specific risk factors in these regions expose their populations to an increased risk of CKD, such as genetic risk with APOL1 among populations of West African heritage or farmers with CKD of unknown etiology that spans various countries across several continents to immigrant/indigenous populations in both low- and high-income countries. Low- and middle-income economies also have the double burden of communicable and noncommunicable diseases, both contributing to the high prevalence of CKD. The economies are characterized by low health expenditure, sparse or nonexistent health insurance and welfare programs, and predominant out-of-pocket spending for medical care. This review highlights the challenges in populations with CKD from low-resource settings globally and explores how health systems can help ameliorate the CKD burden.

Can ACE inhibitors and angiotensin receptor blockers be detrimental in CKD patients?

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.

Pseudohyperkalemia and the Need for Imperative Caution With the Newly Introduced Potent Potassium Binders: Two Cases.

Pseudohyperkalemia was first reported in 1955 by Hartmann and Mellinkoff, as a marked elevation of serum potassium in the absence of clinical evidence of electrolyte imbalance - simultaneous serum potassium exceeds plasma potassium by >0.4 mmol/L. We describe two patients with pseudohyperkalemia who inadvertently received inappropriate potassium binder therapy for weeks to months before the diagnosis of pseudohyperkalemia was entertained and subsequently confirmed. Potassium binders ultimately were promptly discontinued once the diagnosis of pseudohyperkalemia was confirmed. Physicians' attention must be drawn to the availability of the new potent oral potassium binders, patiromer and sodium zirconium cyclosilicate. We strongly advocate for imperative caution with these new binders. Iatrogenic life-threatening hypokalemia remains a real concern and must be avoided. Our patients highlighted the importance of caution in the use of the newer potent potassium binders to mitigate against the causation of iatrogenic hypokalemia. Also as important is the observation that in the same patient, with changing clinical scenarios, a patient might exhibit true hyperkalemia that alternated with pseudohyperkalemia, the first of such a report.

Alternating and Concurrent True Hyperkalemia and Pseudohyperkalemia in Adult Sickle Cell Disease.

Sickle cell disease (SCD) predisposes the patient to recurrent episodes of acute painful hemolytic crisis. Sickle cell nephropathy (SCN) is not uncommon in adult patients, and renal manifestations of SCN include renal ischemia, microinfarcts, renal papillary necrosis, and renal tubular abnormalities with variable clinical presentations. Intravascular hemolysis and reduced glomerular filtration rate with renal tubular dysfunction predispose to true hyperkalemia. Hemolytic crisis can be complicated by sepsis, leading to significant degrees of thrombocytosis, and thrombocytosis is a well-defined cause of pseudohyperkalemia. We describe a 40-year-old African American male patient with sickle cell anemia who exhibited alternating episodes of true hyperkalemia and pseudohyperkalemia, during consecutive hospital admissions. Clearly, true hyperkalemia is a potentially lethal condition. At the same time, the institution of inappropriate and intensive treatment of pseudohyperkalemia leading to severe hypokalemia is also potentially lethal. The need for this caution is most imperative with the recent introduction of the safer and more potent potassium binders, patiromer and sodium zirconium cyclosilicate.

Timed Controlled Repeated Rotation of the CAR-170-C NXSTAGE Chronic Cartridge Hemodialysis Filter: A Novel Approach to Enabling Heparin-Free Frequent Daily Home Hemodialysis.

Heparin-free hemodialysis is often warranted in postoperative states, bleeding diathesis, and critically ill patients. Conventionally, this is achieved through normal saline flushes or regional citrate anticoagulation. An 87-year-old white man with end-stage renal disease and atrial fibrillation, who was taking warfarin and using maintenance home hemodialysis (HHD) with an NxStage machine, underwent laparoscopic appendicectomy. The procedure was complicated by intra-abdominal abscess, sepsis, and tamponade from a bloody pericardial effusion. He needed emergent therapeutic pericardiocentesis. Warfarin was promptly discontinued. He was discharged home with heparin-free HHD. Prior heparin anticoagulation for HHD was an initial bolus of 4000 units of heparin. He continued to clot his extracorporeal system with resultant very high venous pressures and compromised HHD. Heparin anticoagulation was still contraindicated. Flushes with 250-500 mL normal saline, delivered in aliquots every 15-30 minutes, failed to prevent the frequent clotting. The first author, our HD Senior Technician, had astutely observed that the horizontally placed hemodialysis filter exhibited early "clot" formation at the 12-o'clock position, despite the saline flushes. Through trial and error, he discovered that rotating the horizontally placed hemodialysis filter along its long axis, 60 degrees clockwise for 15 minutes, return to the neutral position for 15 minutes, rotating the filter another 60 degrees counterclockwise for 15 minutes, with this repeated cycle of rotations "did the trick." It promptly and consistently resolved the clotting problem. The lines stopped clotting, and he has not needed saline flushes for smooth heparin-free HHD for more than 7 months. To our knowledge, this is the first such report. Further study is justified. We have hypothesized a mechanism and have named this the "Locke-Onuigbo Maneuver."

Clinical Management of Hyperkalemia.

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+) 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+ monitoring, when to reinitiate previously discontinued renin-angiotensin-aldosterone system inhibitor (RAASi) therapy, and when to use oral K+-binding agents. Monitoring serum K+ 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+ 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+ binders may increase confidence in managing patients with hyperkalemia. Lastly, the availability of newer K+-binding agents requires further study to establish whether stringent dietary K+ restrictions are needed in patients receiving K+-binder therapy. Individualized monitoring of serum K+ among patients with an increased risk of hyperkalemia and the use of newer K+-binding agents may allow for optimization of RAASi therapy and more effective management of hyperkalemia.