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.

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.

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.

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.

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.

De novo HBV infection in a Mayo Clinic hemodialysis population: economic impact of reduced HBV testing and a call for changes in current US CDC guidelines on HBV testing protocols.

Hemodialysis (HD) exposes end-stage renal disease patients to significantly higher risks for Hepatitis B Virus (HBV) infection, a major public health scourge. Therefore, current US CDC guidelines, last revised in 2001, call for monthly HbsAg tests. The charge to Medicare per HbsAg test is $100. In an economic analysis, we hypothesized that in the new environment of Medicare Fee Bundling, this is unwise and wasteful if de novo HBV infection rate among HD patients is <1%. We determined de novo HBV infection rate among a Mayo Clinic HD cohort, July 2000-July 2010. A retrospective analysis of all relevant medical records of the cohort was completed to identify de novo HBV infection. Nine hundred sixty-five HD patients were analyzed. One case of de novo HBV infection was identified in a 54-year old known IV drug user, a previous Hepatitis C carrier. This translates to a de novo HBV case incidence rate of 0.1%. De novo HBV infection among HD patients in the US, 2000-2010, is only 0.1%. In the early 1970s, rates were as high as 30%. We recommend 3-monthly HbsAg testing, but to continue current monthly testing for IV drug users and other high-risk groups. Huge cost savings would result, without any compromise of quality outcomes. With over 500,000 HD patients, this represents a mind-boggling $40 billion savings in Medicare charges over 10 years. The US CDC should revise these outdated guidelines, last revised in 2001, to fall in line with current clinical realities on the ground.

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.

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.

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.

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.

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.

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.

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.