The Corrected Serum Sodium Concentration in Hyperglycemic Crises: Computation and Clinical Applications.

In hyperglycemia, hypertonicity results from solute (glucose) gain and loss of water in excess of sodium plus potassium through osmotic diuresis. Patients with stage 5 chronic kidney disease (CKD) and hyperglycemia have minimal or no osmotic diuresis; patients with preserved renal function and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) have often large osmotic diuresis. Hypertonicity from glucose gain is reversed with normalization of serum glucose ([Glu]); hypertonicity due to osmotic diuresis requires infusion of hypotonic solutions. Prediction of the serum sodium after [Glu] normalization (the corrected [Na]) estimates the part of hypertonicity caused by osmotic diuresis. Theoretical methods calculating the corrected [Na] and clinical reports allowing its calculation were reviewed. Corrected [Na] was computed separately in reports of DKA, HHS and hyperglycemia in CKD stage 5. The theoretical prediction of [Na] increase by 1.6 mmol/L per 5.6 mmol/L decrease in [Glu] in most clinical settings, except in extreme hyperglycemia or profound hypervolemia, was supported by studies of hyperglycemia in CKD stage 5 treated only with insulin. Mean corrected [Na] was 139.0 mmol/L in 772 hyperglycemic episodes in CKD stage 5 patients. In patients with preserved renal function, mean corrected [Na] was within the eunatremic range (141.1 mmol/L) in 7,812 DKA cases, and in the range of severe hypernatremia (160.8 mmol/L) in 755 cases of HHS. However, in DKA corrected [Na] was in the hypernatremic range in several reports and rose during treatment with adverse neurological consequences in other reports. The corrected [Na], computed as [Na] increase by 1.6 mmol/L per 5.6 mmol/L decrease in [Glu], provides a reasonable estimate of the degree of hypertonicity due to losses of hypotonic fluids through osmotic diuresis at presentation of DKH or HHS and should guide the tonicity of replacement solutions. However, the corrected [Na] may change during treatment because of ongoing fluid losses and should be monitored during treatment.

An Atypical Presentation of Epstein-Barr Virus Associated Infectious Mononucleosis Mistaken for Pyelonephritis.

Infectious mononucleosis, a syndrome characterized by the triad of pharyngitis, fever, and lymphadenopathy, is caused in the majority of cases by Epstein-Barr virus and usually presents in adolescents and young adults. The disease is for the most part self-limited with full recovery; however, life-threatening complications can occur. Manifestations of Epstein-Barr virus associated infectious mononucleosis can be variable and at times atypical, leading to a delay in diagnosis and consequently unnecessary tests and treatment. We present a case of infectious mononucleosis from Epstein-Barr virus in a female college student who was admitted to the hospital with the initial diagnosis of pyelonephritis. This diagnosis was made based on an abnormal urinalysis, including the presence of white blood cells, red blood cells, and protein, in the setting of high fevers, cough, abdominal pain, left costovertebral tenderness, and an unexplained left neck mass. A monospot was negative two days prior. Renal involvement in Epstein-Barr virus infection is not common and bridges the spectrum from asymptomatic urinary abnormalities to acute renal failure, with acute interstitial nephritis being the most frequent pathological finding. Our patient received corticosteroids and albuterol for a worsening cough, in addition to supportive care. Despite steroid therapy, she developed a debilitating, protracted urticarial rash, also thought to be caused by the Epstein-Barr virus infection. Our case highlights the varied and complex constellation of findings sometimes seen in Epstein-Barr virus infectious mononucleosis. Like in our patient, pharyngitis, a part of the hallmark triad of symptoms characterizing infectious mononucleosis, is not always present, and the monospot may be negative. A high degree of suspicion, as well as recognition that multiple organ systems may be involved in Epstein-Barr virus associated infectious mononucleosis, is required to make the proper diagnosis.

Management of extracellular volume in patients with end-stage kidney disease and severe hyperglycemia.

This commentary addresses volume replacement in hyperglycemic crises in patients with end-stage kidney disease (ESKD). The management of volume issues in this group of patients should not be based on guidelines for management of hyperglycemic crises, but should be individualized and based on directed patient medical history, physical examination, and imaging of the heart and lungs. A scheme for combining information from these three sources is provided.

A Unique Case of Metformin-associated Severe Lactic Acidosis Without Preexisting Renal Disease: Perspectives on Prolonged Dialysis and Education for Prevention.

Metabolic acidosis is a common disorder defined by an imbalance in the body's acid-base balance. Identifying the cause of acidosis is critical for its management. We describe a case of acute renal failure with lactic acidosis in a 69-year-old man who was taking metformin for type 2 diabetes. The patient presented with decreased urine output after two weeks of intermittent nausea and vomiting. During this time, the patient had continued to take limited fluids and medication, including lisinopril and metformin. Physical exam on initial evaluation was remarkable only for hypertension and minimal abdominal tenderness. However, laboratory tests revealed a severe lactic acidosis and renal failure with hyperkalemia. The patient had normal renal function and a normal urine albumin level three weeks prior. Broad-spectrum antibiotics and sodium bicarbonate were administered, followed by hemodialysis. During hemodialysis, the patient became hemodynamically unstable, requiring vasopressors. Post-dialysis, the lactic acidosis worsened, prompting the initiation of additional prolonged dialysis during the first hospital day. After the second lengthy dialysis, the patient's condition improved significantly and he was discharged on hospital day 12, with the diagnosis of metformin-associated lactic acidosis (MALA) in the setting of acute tubular necrosis from gastrointestinal fluid loss accompanied by the continued use of an angiotensin-converting enzyme inhibitor. After discharge, his renal function returned to normal. Severe lactic acidosis from metformin is relatively rare. Metformin has a large volume of distribution and accumulates in erythrocytes and intestinal cells, resulting in less efficient removal with dialysis and rebound lactic acidosis. Prolonged dialysis may be necessary for MALA to improve outcomes. Identifying metformin levels may help in diagnosis and management. However, the means to Identify metformin levels are not widely available. Patients receiving metformin should be counseled to stop metformin and seek medical care in the setting of illnesses. This is particularly important given the frequency of metformin prescription and the common use of renin-angiotensin system blockade in patients with type 2 diabetes, which increases the risk of kidney dysfunction.

Dialysis-associated hyperglycemia: manifestations and treatment.

PURPOSE: Dialysis-associated hyperglycemia (DAH), is associated with a distinct fluid and electrolyte pathophysiology. The purpose of this report was to review the pathophysiology and provide treatment guidelines for DAH. METHODS: Review of published reports on DAH. Synthesis of guidelines based on these reports. RESULTS: The following fluid and solute abnormalities have been identified in DAH: (a) hypoglycemia: this is a frequent complication of insulin treatment and its prevention requires special attention. (b) Elevated serum tonicity. The degree of hypertonicity in DAH is lower than in similar levels of hyperglycemia in patients with preserved renal function. Typically, correction of hyperglycemia with insulin corrects the hypertonicity of DAH. (c) Extracellular volume abnormalities ranging from pulmonary edema associated with osmotic fluid shift from the intracellular into the extracellular compartment as a consequence of gain in extracellular solute (glucose) to hypovolemia from osmotic diuresis in patients with residual renal function or from fluid losses through extrarenal routes. Correction of DAH by insulin infusion reverses the osmotic fluid transfer between the intracellular and extracellular compartments and corrects the pulmonary edema, but can worsen the manifestations of hypovolemia, which require saline infusion. (d) A variety of acid-base disorders including ketoacidosis correctable with insulin infusion and no other interventions. (e) Hyperkalemia, which is frequent in DAH and is more severe when ketoacidosis is also present. Insulin infusion corrects the hyperkalemia. Extreme hyperkalemia at presentation or hypokalemia developing during insulin infusion require additional measures. CONCLUSIONS: In DAH, insulin infusion is the primary management strategy and corrects the fluid and electrolyte abnormalities. Patients treated for DAH should be monitored for the development of hypoglycemia or fluid and electrolyte abnormalities that may require additional treatments.

Chronic Nephropathy from Dietary Hyperoxaluria: Sustained Improvement of Renal Function after Dietary Intervention.

A 56-year-old man with stable chronic kidney disease (CKD) for two years following a single episode of calcium oxalate urolithiasis developed progressive elevation of his serum creatinine concentration. Urinalysis revealed pyuria and white cell casts, a few red blood cells, minimal proteinuria, and no crystals. Urine culture was sterile. Gallium scintigraphy was consistent with interstitial nephritis. Proton pump inhibitor intake was discontinued, and a short course of oral corticosteroids was initiated. Percutaneous kidney biopsy, performed because of the continued deterioration of renal function to a minimum estimated glomerular filtration rate (eGFR) value of 15 mL/min per 1.73 m2 and persistent pyuria, revealed deposition of oxalate crystals in the tubules and interstitium, pronounced tubular changes, and interstitial nephritis and fibrosis. Urinary oxalate excretion was very high, in the range usually associated with primary hyperoxaluria. However, investigations for primary or enteric hyperoxaluria were negative. He reported a diet based on various nuts high in oxalate content. Estimated oxalate content in the diet was, for years, approximately four times higher than that in the average American diet. The institution of a diet low in oxalates resulted in the rapid normalization of urinary oxalate excretion and urinary sediment and in the slow, continuous improvement of renal function to near normal levels (eGFR 59 mL/min/1.73 m2) before his death from a brain malignancy 3.5 years later. The manifestations of nephropathy secondary to dietary hyperoxaluria, including the urine findings, can be indistinguishable from other types of interstitial nephritis. The diagnosis of dietary hyperoxaluria requires careful dietary history and a kidney biopsy. Identifying dietary hyperoxaluria as the cause of CKD is important because the decrease in dietary oxalate intake without any other measures can lead to sustained improvement in renal function.

Vascular Access Site for Renal Replacement Therapy in Acute Kidney Injury: A Post hoc Analysis of the ATN Study.

BACKGROUND: Acute kidney injury requiring renal replacement therapy (RRT) in the intensive care unit portends a poor prognosis. The decisions regarding dialysis catheter placement is based mainly on physician discretion with little evidence to support the choice of dialysis catheter location. METHODS: The Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network Study was a multicenter, prospective, randomized trial of intensive vs. less intensive RRT in critically ill patients with AKI. We assessed the association of dialysis catheter location with dialysis catheter-related outcomes including catheter-related complications, mortality, dialysis dependence, and dialysis dose delivered. RESULTS: Of the 1,124 patients enrolled in the ATN study, catheter data were available in 1,016 (90.39%) patients. A total of 91 (8.96%) subclavian, 387 (38.09%) internal jugular, and 538 (52.95%) femoral dialysis catheters were inserted. The femoral group was younger (58.39 ± 16.27), had greater bleeding tendency [lower platelet count (96.00 ± 109.35) with higher INR (2.01 ± 2.19)], and had a higher baseline sequential organ failure assessment score on admission (14.59 ± 3.61) compared to the other two groups. Dialysis catheter-related complications were low in this study with no significant difference in the rates of complications among all catheter locations. Mortality and dialysis dependence was lowest in the subclavian group, while the dose of dialysis delivered (Kt/V) remained lowest in the femoral group, after propensity score and center adjustments. CONCLUSION: Patient characteristics influence the choice of dialysis catheter location with a tendency to place femoral catheters in younger, sicker, and more coagulopathic patients. There were no statistically significant differences in complication rates among the three catheter locations, although femoral catheters may be associated with a lower delivered dose of dialysis during intermittent hemodialysis. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT00076219.

BK nephropathy in the native kidneys of patients with organ transplants: Clinical spectrum of BK infection.

Nephropathy secondary to BK virus, a member of the Papoviridae family of viruses, has been recognized for some time as an important cause of allograft dysfunction in renal transplant recipients. In recent times, BK nephropathy (BKN) of the native kidneys has being increasingly recognized as a cause of chronic kidney disease in patients with solid organ transplants, bone marrow transplants and in patients with other clinical entities associated with immunosuppression. In such patients renal dysfunction is often attributed to other factors including nephrotoxicity of medications used to prevent rejection of the transplanted organs. Renal biopsy is required for the diagnosis of BKN. Quantitation of the BK viral load in blood and urine are surrogate diagnostic methods. The treatment of BKN is based on reduction of the immunosuppressive medications. Several compounds have shown antiviral activity, but have not consistently shown to have beneficial effects in BKN. In addition to BKN, BK viral infection can cause severe urinary bladder cystitis, ureteritis and urinary tract obstruction as well as manifestations in other organ systems including the central nervous system, the respiratory system, the gastrointestinal system and the hematopoietic system. BK viral infection has also been implicated in tumorigenesis. The spectrum of clinical manifestations from BK infection and infection from other members of the Papoviridae family is widening. Prevention and treatment of BK infection and infections from other Papovaviruses are subjects of intense research.

Prolonged hypernatremia triggered by hyperglycemic hyperosmolar state with coma: A case report.

A man with past lithium use for more than 15 years, but off lithium for two years and not carrying the diagnosis of diabetes mellitus or nephrogenic diabetes insipidus (NDI), presented with coma and hyperglycemic hyperosmolar state (HHS). Following correction of HHS, he developed persistent hypernatremia accompanied by large volumes of urine with low osmolality and no response to desmopressin injections. Urine osmolality remained < 300 mOsm/kg after injection of vasopressin. Improvement in serum sodium concentration followed the intake of large volumes of water plus administration of amiloride and hydrochlorothiazide. Severe hyperglycemia may trigger symptomatic lithium-induced NDI years after cessation of lithium therapy. Patients with new-onset diabetes mellitus who had been on prolonged lithium therapy in the past require monitoring of their serum sodium concentration after hyperglycemic episodes regardless of whether they do or do not carry the diagnosis of NDI.