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.

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.

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.

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.

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.

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.

Incidence of chromosomal abnormalities in bovine blastocysts derived from unsorted and sex-sorted spermatozoa.

The aim of the present study was to examine the incidence of chromosomal abnormalities in bovine blastocysts produced by IVF with unsorted, X-sorted or Y-sorted spermatozoa. In Experiment 1, individual blastocysts were processed to examine the incidence of mixoploidy using fluorescent in situ hybridisation. Overall, 80% (44/55) of blastocysts were mixoploid (10/15, 14/15 and 20/25 for X-sorted, Y-sorted and unsorted spermatozoa, respectively; P > 0.05). However, the prevalence of abnormal XY chromosome complements was relatively low in all groups; on average, only a small fraction of the total nuclei per embryo appeared polyploid (1.64%, 5.62% and 6.0% for X-sorted, Y-sorted and unsorted spermatozoa, respectively). Interestingly, 20% (5/25) of blastocysts derived from unsorted spermatozoa were found to be chimeric (XX/XY). In Experiment 2, chimeric embryos were detected among the blastocysts derived from two of five sires tested. In addition, one chimeric blastocyst was detected among nine in vivo-derived blastocysts obtained following AI. In conclusion, based on the results of the present study, the incidence of chromosomal abnormalities did not different between blastocysts derived from sex-sorted or unsorted spermatozoa. In addition, the occurrence of mixed sex chimeras was not limited to a single sire and was not unique to blastocysts derived from IVF.

Newly symptomatic central diabetes insipidus in ESRD with adult polycystic kidney disease following intracranial hemorrhage: the first reported case.

BACKGROUND: Adult polycystic kidney disease (ADPKD), an autosomal dominantly inherited cause of ESRD, is often characterized by a relative renal tubular unresponsiveness to ADH. Polyuria, renal concentrating defects and generally elevated ADH levels, a form of nephrogenic diabetes insipidus (NDI) is often implicated. Thus, even late in stages of CKD, ADPKD patients often produce significant amounts of urine. Conversely, central diabetes insipidus (CDI), a clinical syndrome secondary to deficiency of ADH, also leads to production of large volumes of dilute urine, i.e. polyuria. It is widely believed that clinical CDI is masked in ESRD patients on dialysis, due to apparently obvious reasons. However, there have been published a few reports of the unmasking of polyuria secondary to previously existing CDI in ESRD patients, after kidney transplantation. CASE REPORT: We report, to our knowledge, the first case of new-onset symptomatic CDI causing nocturnal polyuria in an ADPKD patient with ESRD, before now on hemodialysis. CDI symptoms were noted, months after an intracranial aneurysm clipping procedure that was complicated by intra-cranial hemorrhage. The 59-year old Caucasian woman responded moderately to desmopressin replacement therapy. CONCLUSIONS: Several interesting pathobiologic implications of this case report are entertained.

Syndrome of rapid-onset end-stage renal disease: a new unrecognized pattern of CKD progression to ESRD.

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.

Bilateral lower extremity sequential compression devices (SCDs): a novel approach to the management of intra-dialytic hypotension in the outpatient setting--report of a case series.

Intra-dialytic hypotension (IDH) affects as many as 15-50% of patients during hemodialysis. Several treatment approaches and preventative methods are available. These therapeutic options are often ineffective and cumbersome, and some of the causative factors such as poor cardiac reserve are commonly not amenable to any therapy. Enhanced external counter pulsation (EECP) is increasingly being utilized by cardiology services as an adjunct to the long-term management of chronic congestive heart failure as well as in the management of otherwise refractory angina. EECP works by mechanistically improving venous return, enhancing peripheral resistance, and ultimately improving the cardiac index. We speculated that bilateral lower extremity sequential compression devices (SCDs), commonly used in the inpatient setting for DVT prophylaxis, could indeed serve as mini-EECP devices. We carried out an outpatient pilot study of its use to prevent IDH in three patients who otherwise had failed other treatment approaches. The SCDs were effective, convenient, and safe. We were able to achieve ultrafiltration (UF) goals of 1-3 kg during hemodialysis sessions in all three patients, consistently, for months, a feat that was not possible previously. This novel modality of managing IDH is complementary to other standard therapies. Larger multi-center studies are warranted.

Hepatitis B surface antigenemia following recombinant Engerix B hepatitis B vaccine in an 81-year-old ESRD patient on hemodialysis.

The first cases of transient hepatitis B surface antigenemia (HBsAg) in adults following hepatitis B virus (HBV) immunization were reported in the 1990s. HBV immunization is mandatory for all hemodialysis (HD) patients. Ly et al. who demonstrated transient HBsAg in eight out of nine HD patients following HBV vaccine concluded that HD patients should not be screened for HBV within a week of HBV immunization and that positive HBsAg within a month of HBV immunization must be interpreted with caution. We present an 81-year-old woman on HD, who needed a booster Recombivax (Merck, Whitehouse Station, NJ, USA) vaccine after remaining hepatitis B surface antibody (HBsAb) negative from previous vaccinations. The HD Unit had switched to Engerix B (GlaxoSmithKline, Atlanta, GA, USA) HBV vaccine. Two days after the first Engerix B vaccine, HBsAg was detected. She was asymptomatic; ALT was 25 U/L. Repeat testing for HBsAg, HBsAb, hepatitis B E antigen (HB E Ag), and hepatitis B DNA (HB DNA), a week later, all returned negative. Previous reports of transient HBsAg following HBV vaccines were after Engerix B vaccination. Our patient is unusual since she had received both brands of HBV vaccines, sequentially, at different times. Twice, HBsAg tests completed as early as 5 days following Recombivax vaccine were negative. We submit that positive HBsAg tests are more likely following Engerix B vaccines. We reemphasize previous recommendations that patients should not be screened for HBsAg < 4 weeks following HBV immunization. This is particularly important in HD units where hepatitis B screening is carried out routinely all year round and hepatitis B vaccinations are commonplace. Very strict schedules must be adopted to avoid false positive HBsAg tests.

Non-dilated obstructive uropathy - an unrecognized cause of acute renal failure in hospitalized US patients: three case reports seen over 6 months in a northwestern Wisconsin nephrology practice.

The syndrome of non-dilated obstructive uropathy (NDOU) and acute renal failure (ARF) is well reported. However, the literature suggests that this syndrome is rare, accounting for less than 5% of cases of urinary obstruction. Our recent experience with three cases of NDOU seen within a space of months implies otherwise. Between March 2009 and October 2009, in a small Midwestern American town Nephrology practice, we successfully managed three cases of NDOU. They all presented with newly symptomatic ARF. Renal imaging revealed no dilatation in both kidneys in one, only unilateral dilatation in the second, and dilatation was absent in a single functioning kidney in the third. They comprised of two males and one female, mean age 61 years (peak creatinine: 320-880 µmol/L). Despite the absence of dilatation on renal imaging, strong suspicion for NDOU led to decompression procedures with prompt recovery of kidney function in all three patients - two required percutaneous nephrostomy tube placements and/or ureteric stents and one responded to simple Foley catheter drainage. One required temporary hemodialysis. We submit that NDOU may be more common than previously speculated. A high index of suspicion is warranted as significant renal salvage can often be achieved by timely decompression procedures.

Page Kidney Complicating Kidney Biopsy after Stopping Apixaban: A Physician's Dilemma.

Page kidney was described by Page, following very elaborate experiments with animal kidneys in 1939, with persistent arterial hypertension from "cellophane perinephritis." Subsequently, it was reported after trauma, from renal cysts and tumors, and from intrarenal hematoma complicating percutaneous kidney biopsy. We describe Page kidney associated with acute kidney injury 26 days after an uncomplicated ultrasound-guided right native kidney biopsy. Patient was on Apixaban, a non-vitamin K antagonist oral anticoagulant (NOAC) for atrial fibrillation which was withheld 3 days before the procedure. It was restarted 3 days after. The evidence-base supporting guidelines and recommendations for the peri-procedural management of the NOACs is inadequate, sparse, and often conflicted. More research is warranted.

Post-Renal Biopsy Acute Kidney Injury and Page Kidney from Intra-Renal Hematoma Aggravated by Reversible Contrast-Induced Nephropathy Following Renal Arterial Embolization.

BACKGROUND Page kidney was described by Dr. Irving Page in animal kidneys in 1939 with renal failure and persistent arterial hypertension from "cellophane perinephritis". By 2009, about 100 cases of Page kidney had been reported. Bleeding complications after percutaneous kidney biopsy has, however, been well described. Moreover, the perioperative management of the recently introduced non-vitamin K antagonist anticoagulants (NOACs) remains uncertain due to inadequate evidence. Current guidelines to determine the appropriate duration of withholding NOACs before a surgical procedure, and when to restart NOACs safely after a procedure, however, cognizant of the implications of renal dysfunction, and levels of risk of the procedure are still unclear and sometimes conflicted. CASE REPORT We describe a case of Page kidney from an intrarenal hematoma complicating ultrasound-guided percutaneous right native kidney biopsy with acute kidney injury after withholding apixaban, a NOAC, for 3 days. Computed tomography evidence of continuing intrarenal bleeding from a renal pseudoaneurysm was treated with super-selective renal artery embolization; the case was further complicated by superimposed acute kidney injury from contrast-induced nephropathy. CONCLUSIONS We reviewed the vagaries of Page kidney with respect to the presence, or otherwise, of hypertension and how to explain worsening renal failure despite only unilateral involvement of a single kidney in a patient with 2 kidneys. Furthermore, we revisit the risks of contrast-induced nephropathy following iodinated contrast exposure. We explored the alternative management options for a post-biopsy renal pseudoaneurysm, that would avoid the use of iodinated contrast that could have potentially mitigated, if not fully prevented, the ensuing contrast-induced acute kidney injury.

Analytical review of the evidence for renoprotection by renin-angiotensin-aldosterone system blockade in chronic kidney disease - a call for caution.

Despite reported renoprotection with angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), and notwithstanding their increased use, we continue to experience an epidemic of acute renal failure (ARF)/chronic kidney disease/end-stage renal disease. Consequently, concerns about iatrogenic renal failure have resurfaced. Different analysis of these trials revealed flaws such as recruitment of relatively younger patients with preserved baseline renal function, common utilization of lower end doses of ACEIs/ARBs, high drug discontinuation rates, excessive use of surrogate endpoints, inadequate reporting of adverse effects, and short duration studies. Again, lower 24-hour ambulatory blood pressure among patients in the ramipril arm of the micro-HOPE (Heart Outcomes Prevention Evaluation) study raises doubts of renoprotection beyond blood pressure lowering. The disappointing results from the ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) study only compounded these doubts. We demonstrated significant renal salvage after ACEI/ARB was discontinued in chronic kidney disease patients recruited with increasing ARF while on ACEI/ARB. Apart from our reports, there are increasing reports incriminating the use of ACEI/ARB with ARF exacerbations. We conclude that close and indefinite monitoring of estimated glomerular filtration rate is an absolute must in these patients. The treating physician must be ready to consider trial discontinuation of ACEI/ARB, promptly. Combination ACEI + ARB therapy should be the exception, rather than the rule. Temporary withdrawal of ACEI/ARB before certain exposures, 'renoprevention', would only further improve the results of renoprotection.

The natural history of chronic kidney disease revisited--a 72-month Mayo Health System Hypertension Clinic practice-based research network prospective report on end-stage renal disease and death rates in 100 high-risk chronic kidney disease patients: a call for circumspection.

The natural history of chronic kidney disease (CKD), in general, remains conjectural. Current literature on rates of progression to end-stage renal disease (ESRD) as compared with mortality in CKD shows conflicts. A study of 27,998 patients in managed care reported a 5-year ESRD rate of 20% and a death rate of 50%. In 1666 patients in the Modification of Diet in Renal Disease study, a much higher ESRD rate of 60% after 88 months was reported (four times the death rate); among patients older than 65 years, the death rate approximated the ESRD rate. More than 20 million Americans have CKD [estimated glomerular filtration rate (eGFR) < 60 mL/min). Annually, approximately 100,000 new U.S. patients develop ESRD, accounting for a casual annual ESRD rate of only 0.5% among the U.S. CKD population. Similarly, this author's anecdotal experience suggests a more benign CKD outcome than is suggested by the two foregoing studies. A 72-month prospective report of an aging cohort of 100 CKD patients, high risk because they all experienced acute kidney injury at study entry, is presented. The finding of an approximately 18% ESRD rate and 13% death rate after 4 years contrasts sharply with the two studies cited earlier. Several factors--prospective as compared with retrospective analysis, varying patient age and other variables, managed care as compared with other care, and other unknown variables--play important roles in CKD outcome. This author agrees with researchers who recently emphasized the heterogeneity of the CKD population. Patient prognosis and management must be individualized.

Drug-induced encephalopathy secondary to non renal dosing of common medications in Two dialysis patients.

The U.S. end-stage renal disease (ESRD) population continues to increase. Adjustment of several drugs administered to dialysis patients is mandatory because of decreased--and sometimes totally absent--renal clearances. Gabapentin, a newer anticonvulsant increasingly used for several other clinical indications, is excreted in the urine unchanged. Its half-life of 5 - 9 hours is increased to up to 132 hours in anuric patients. Excretion of acyclovir an antiviral agent, occurs predominantly through the kidney (glomerular filtration and tubular secretion). Its normal plasma half-life is 2 - 3 hours; dosage modifications are obligatory in renal insufficiency. In 2008, we encountered 2 ESRD patients on dialysis who exhibited significant neurotoxicity with encephalopathy after gabapentin and acyclovir were given at the usual adult doses. Following prompt drug discontinuation and continued daily hemodialysis or peritoneal dialysis respectively, both patients were discharged home, in normal clinical condition, after 3 days. With the increasing ESRD (and CKD) populations, health care providers other than nephrologists will have increasing contact with these patients. Those providers must consider drug dose modifications according to residual renal function. Algorithms for appropriate renal drug dosing are available from various sources. Pragmatic tactics of this kind will avoid significant morbidity and mortality. In addition, this approach will save millions of now increasingly scarce health care dollars.