The global burden imposed by metabolic diseases and associated complications continue to escalate. Neurological complications, most commonly peripheral neuropathy, represent a significant cause of morbidity and disability in patients with diabetes and chronic kidney disease. Furthermore, health care costs are substantially increased by the presence of complications making investigation into treatment a matter of high priority. Over the last decade nerve excitability techniques have entered the clinical realm and enabled in vivo assessment of biophysical properties and function of peripheral nerves in health and disease. Studies of excitability in diabetic neuropathy have demonstrated alteration in biophysical properties, including changes in Na(+) conductances and Na(+)/K(+) pump function, which may contribute to the development of neuropathic symptoms. Interventional studies have demonstrated that these changes are responsive to pharmacological agents. Excitability studies in patients with chronic kidney disease have demonstrated prominent changes that may contribute to the development of uraemic neuropathy. In particular, these studies have demonstrated strong correlation between hyperkalaemia and the development of nerve dysfunction. These studies have provided a basis for future work assessing the benefits of potassium restriction as a therapeutic strategy in this condition.

We report a newborn girl with life-threatening hyperkalemia and salt wasting crisis due to severe autosomal recessive multiple target organ dysfunction pseudohypoaldosteronism type 1 (MTOD PHA1). She was aggressively managed with intravenous fluids, potassium-lowering agents, high-dose sodium chloride supplementation and peritoneal dialysis. Genetic analysis revealed a homozygous mutation of the a- ENaC (epithelial Na+ channel) gene. She had a stormy clinical course with refractory hyperkalemia and prolonged hospitalization. Eventually, she succumbed to pneumonia and septicemia at 4 months of age. This is probably the first case of PHA1 confirmed by genetic analysis from India.

Uncontrolled elevation in plasma potassium within minutes of rapid blood volume loss is associated with mortality and distinguishes non-survivors of severe hemorrhage from survivors. In a pig model of severe hemorrhage, we discovered that along with a sharp increase in plasma potassium co-incident with a shut down of urine flow, non-survivors also had an insufficient vasopressin response to hemorrhage. In contrast, survivors did have elevated vasopressin levels in response to hemorrhage and maintained plasma potassium within normal limits. While it has been demonstrated for some time that vasopressin can influence secretion of potassium in the distal nephron, the magnitude of this effect and conditions under which this contributes to physiological modulation of potassium excretion has yet to be defined. In this review, we assess the evidence that would suggest that vasopressin plays a key role in modulating potassium excretion and is important in the regulation of potassium homeostasis during hemorrhage.

Laboratory research and previous study suggest that aliskiren, a direct renin inhibitor, has anti-proteinuric effects. We conducted a randomized crossover study to evaluate the anti-proteinuric effect of aliskiren in patients with immunoglobulin A (IgA) nephropathy.We studied 22 patients with biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Patients were randomized to either oral aliskiren 300 mg/day or placebo for 16 weeks and then crossed over to the other treatment arm after a washout period. Proteinuria, estimated glomerular filtration rate (eGFR), blood pressure, and serum potassium were monitored.After aliskiren treatment, there was a significant reduction in proteinuria in 4 weeks (1.76±0.95 to 1.03±0.69 g:g-Cr, p<0.0001), which remained at a low level throughout the treatment period. There was a significant difference in proteinuria between the aliskiren and placebo groups from 4 to 16 weeks after treatment (p<0.01 for all comparisons). After aliskiren treatment, there were modest but statistically significant reductions in eGFR (57.2±29.1 to 54.8±29.3 ml/min/1.73 m(2), p = 0.013) and diastolic blood pressure (72.6±12.3 to 66.2±11.2 mmHg, p<0.0001). None of the patient developed severe hyperkalemia (serum potassium ≥6.0 mmol/l) during the study period.Aliskiren has anti-proteinuric effect in patients with IgA nephropathy and persistent proteinuria despite ACE inhibitor or ARB. Further studies are needed to confirm the renal protecting effect of direct renin inhibition in chronic proteinuric kidney diseases.ClinicalTrials.gov NCT00870493.

BACKGROUND:

Reasons underlying dialysis decision-making in Octogenarians and Nonagenarians have not been further explored in prospective studies.

METHODS:

This regional, multicentre, non-interventional and prospective study was aimed to describe characteristics and quality of life (QoL) of elderly (>=80 years of age) with advanced chronic kidney disease (stage 3b-5 CKD) newly referred to nephrologists. Predictive factors of death and dialysis initiation were also assessed using competing-risk analyses.

RESULTS:

All 155 included patients had an estimated glomerular filtration rate (eGFR) below 45 ml/min/1.73m2. Most patients had a non anaemic haemoglobin level (Hb) with no iron deficiency, and normal calcium and phosphate levels. They were well-fed and had a normal cognitive function and a good QoL. The 3-year probabilities of death and dialysis initiation reached 27% and 11%, respectively. The leading causes of death were cardiovascular (32%), cachexia (18%), cancer (9%), infection (3%), trauma (3%), dementia (3%), and unknown (32%). The reasons for dialysis initiation were based on uncontrolled biological abnormalities, such as hyperkalemia or acidosis (71%), uncontrolled digestive disorders (35%), uncontrolled pulmonary or peripheral oedema (29%), and uncontrolled malnutrition (12%). No patients with acute congestive heart failure or cancer initiated dialysis. Predictors of death found in both multivariate regression models (Cox and Fine & Gray) included acute congestive heart failure, age, any walking impairment and Hb <10g/dL. Regarding dialysis initiation, eGFR <23mL/min/1.73m2 was the only predictor found in the Cox multivariate regression model whereas eGFR <23mL/min/1.73m2 and diastolic blood pressure were both independently associated with dialysis initiation in the Fine & Gray analysis. Such findings suggested that death and dialysis were independent events.

CONCLUSIONS:

Octogenarians and Nonagenarians newly referred to nephrologists by general practitioners were highly selected patients, without any symptoms of the common geriatric syndrome. In this population, nephrologists' dialysis decision was based exclusively on uremic criteria.

BACKGROUND:

Hypophosphatemia occurs in about 25% of patients admitted to the intensive care unit. To date, a safe and validated phosphate replacement protocol is not available.

OBJECTIVE:

To evaluate an individualized phosphate replacement regimen.

DESIGN:

Fifty consecutive intensive care unit patients with a serum phosphate level <0.6 mmol/L were treated with sodium-potassium-phosphate intravenously at a rate of 10 mmol/h. The dose was calculated according to the following equation: Phosphate dose in mmol = 0.5 × Body Weight × (1.25 - [serum Phosphate]). Phosphate levels were measured immediately upon completion of the infusion, as well as the next morning at 8 am.

RESULTS:

Post-infusion phosphate levels were >0.6 mmol/L in 98% of the patients. Hyperphosphatemia, hyperkalemia or a decrease in serum calcium were not observed. In about a third of patients serum phosphate decreased to <0.6 mmol/L within the next 24 hours after infusion. The phosphate distribution volume calculated from the results of infusion and corrected for renal phosphate loss during the infusion period was 0.51 L/kg (95% CI 0.42-0.61 L/kg).

CONCLUSION:

This study shows that phosphate replacement with dose calculation based on serum phosphate levels and a Vd of 0.5 L/kg is effective and safe.

CME EDUCATIONAL

OBJECTIVES

1.Describe the varying clinical presentations of pseudohypoaldosteronism in the neonatal period.2.Review the physiology of aldosterone production and pathophysiology of pseudohypoaldosteronism.3.Identify treatment options for pseudohypoaldosteronism when identified in the neonatal period. Pseudohypoaldosteronism type I (PHA1) is a rare disease of mineralocorticoid resistance caused by defects in sodium transport in the distal tubule of the kidney. It presents in the neonate with life-threatening dehydration due to salt wasting, accompanied by hyperkalemia, acidosis, and, frequently, failure to thrive. Patients with PHA1 are often initially diagnosed with congenital adrenal hyperplasia, but their electrolyte abnormalities are resistant to treatment with glucocorticoids and mineralocorticoids. In these patients, an astute clinician will broaden his or her differential, resulting in life-saving treatment.

This study aimed to report on a toddler who presented with progressively worsening abdominal pain and obstructive uropathy 1 week after ureteral valve reimplantation. Acute renal failure resulted in critical hyperkalemia.Chart review of presentation, physical examination, laboratory tests, and treatment.Initial potassium level was 10 mEq/L; ventricular tachycardia was observed and treated.More commonly, hyperkalemia results from overuse/overdose of supplementation or in patients with known renal failure. Although less common, obstructive uropathy should be considered in any patient with recent instrumentation of the urinary tract and coincident complications can be significant.

BACKGROUND:

Cardiac arrest patients often suffer from dysfunction of multiple organ systems after return of spontaneous circulation (ROSC). The incidence of renal dysfunction in patients with out-of-hospital cardiac arrest (OHCA) is not well described. Renal dysfunction has been associated with worse outcomes in critical illness.

HYPOTHESIS:

Renal dysfunction is common after OHCA, and renal dysfunction is independently associated with survival.

METHODS:

We performed a retrospective review of consecutive adult patients admitted to an intensive care unit after successful resuscitation from OHCA between 01/01/2005 and 12/31/2010. Patients were excluded for death or withdrawal of care within 24h, preexisting end-stage renal disease, or OHCA due to hyperkalemia. The RIFLE criteria were used to classify subjects with renal dysfunction into one of three categories - risk, injury, or failure - based on trending of serum creatinine concentration or glomerular filtration rate. Data were analyzed using descriptive statistics.

RESULTS:

Of 364 patients, 38 were excluded due to death or withdrawal of care within 24h, 11 due to end-stage renal disease, and 4 due to OHCA from hyperkalemia, leaving 311 patients in the final analysis. The mean age was 58 (SD 16) years; 174 (59%) were male, VF/VT was the primary rhythm in 156 (50%), and 236 (80%) were comatose at hospital arrival. Among 311 patients, 32 (10.3%) developed acute renal failure (ARF), 27 (8.7%) developed acute kidney injury (AKI), and 56 (18.0%) developed risk of renal dysfunction. Of the 32 subjects that developed ARF, renal replacement therapy (RRT) was initiated on 13 (40.6%). Development of ARF was not associated with survival (OR 0.73; 95% CI 0.26, 2.05) after adjusting for initial rhythm or illness severity.

CONCLUSIONS:

More than one-third of patients resuscitated from OHCA developed evidence of renal dysfunction, and 19% of patients meeting criteria for AKI or ARF. In this study, development of renal failure was not independently associated with survival.

Background:

Hyperkalemia has multimodal effects on myocardial protection during ischemia/reperfusion. The preservation of Na(+)/K(+)-ATPase activity induced by hyperkalemia may have critical impact on myocardial protection.

Methods:

To elucidate the roles of hyperkalemia (16 mM) and Na(+)/K(+)-ATPase inhibition (100 µM ouabain) in myocardial protection during simulated ischemia (5 mM NaCN and 5.5 mM 2-deoxyglucose)/reperfusion, we measured loss of membrane integrity and bleb formation using a vital dye calcein AM in cultured neonatal rat cardiomyocytes. The control perfusate was switched to treatment solution for 15 min, followed by reperfusion for 30 min. In a second set of experiments, myocardial excitability and diastolic intracellular calcium ion concentration ([Ca(2+)]i) were measured during a 45-min treatment using a calcium-sensitive fluorescent dye fluo-4 AM.

Results:

Simulated ischemia/reperfusion under ouabain treatment induced loss of membrane integrity, which was suppressed by hyperkalemia. Simulated ischemia/reperfusion induced bleb formation, which was accelerated by ouabain. Hyperkalemia delayed and inhibited the increase in diastolic [Ca(2+)]i induced by simulated ischemia. Furthermore, hyperkalemia almost completely inhibited the effects of ouabain on the diastolic [Ca(2+)]i during ischemia.

Conclusions:

These results suggest that hyperkalemia during ischemia is cardioprotective against ischemia/reperfusion insults and that hyperkalemia inhibits the effects of ouabain during ischemia. J. Med. Invest. 60: 66-76, February, 2013.