Search

BACKGROUND Hemodialysis corrects metabolic acidosis by transferring bicarbonate or bicarbonate equivalents across the dialysis membrane from the dialysis fluid to the plasma. With the conventional three-stream bicarbonate-based dialysis fluid delivery system, a change in the bicarbonate concentration results in changes in the other electrolytes. In practice, the dialysis machine draws either a little less or more from the bicarbonate concentrate and a little more or less from the acid concentrate, respectively in a three-stream delivery system. The result not only changes the bicarbonate concentration of the final dialysis fluid but also causes a minor change in the other ingredients. METHODS We propose a four-stream bicarbonate-based dialysis fluid delivery system consisting of an acid concentrate, a base concentrate, a product water, and a new sodium chloride concentrate. RESULTS By adjusting the flow rate ratio between the sodium chloride and sodium bicarbonate concentrates, one can achieve the desired bicarbonate concentration in the dialysis fluid without changing the concentration of sodium or ingredients in the acid concentrate. The chloride concentration mirrors the change in bicarbonate but in the opposite direction. CONCLUSION A four-stream, bicarbonate-based dialysis fluid delivery system allows the bicarbonate concentration to be changed without changing the other constituents of the final dialysis fluid.

We propose a new 45X, four-stream, triple-concentrate, bicarbonate-based dialysis fluid delivery system, allowing a wide range of dialysis fluid sodium concentrations\\ (DFNa ) without affecting the concentrations of other crucial solutes. The four streams consist of product water (W), and concentrates with sodium chloride (S), acid (A), and sodium bicarbonate (B). An adjustment in the DFNa in this new system requires changes only in the W and S concentrate streams. The ingredients in A and B concentrates do not change.

Herbal medicine, a form of complementary and alternative medicine (CAM), is used throughout the world, in both developing and developed countries. The ingredients in herbal medicines are not standardized by any regulatory agency. Variability exists in the ingredients as well as in their concentrations. Plant products may become contaminated with bacteria and fungi during storage. Therefore, harm can occur to the kidney, liver, and blood components after ingestion. We encourage scientific studies to identify the active ingredients in herbs and to standardize their concentrations in all herbal preparations. Rigorous studies need to be performed in order to understand the effect of herbal ingredients on different organ systems as well as these substances' interaction with other medications.

A man with systemic sclerosis (SS), manifested by characteristic skin lesions, gastro-esophageal reflux disease, and pulmonary fibrosis producing progressive respiratory failure, and a positive antinuclear antibody consistent with reactivity to fibrillarin, developed skin lesions with the clinical and histological characteristics of lupus erythematosus tumidus (LET) 10 years after the diagnosis of SS. His respiratory failure progressed and he expired from sepsis after tracheal intubation and mechanical ventilation two years after developing LET. The association of SS and LET, not described until now, raises questions about its pathogenesis and its prognostic significance.

Hypertension is one of the commonest cause of chronic kidney disease (CKD) in Nigerians. We describe blood pressure (BP) control and kidney disease markers in patients with hypertension as part of measures to curb the burden of this chronic debilitating disease.Patients with hypertension in the main tertiary hospitals in three states in north central Nigeria were evaluated for indicators of CKD, including proteinuria and estimated glomerular filtration rate (eGFR)60 ml/min/1.73 mA total of 1063 subjects (63.1% females and 36.8% males) with a mean age of 55 ± 11 years were studied. Diabetes mellitus (DM) was present in 214 (20.6%) and 422 (39.7%) had optimal BP control. The median duration of hypertension was 6 years (range 1-44 years). Proteinuria occurred in 130 (12.2%), while 212 (19.9%) had reduced eGFR and 46 (4.3%) had proteinuria and reduced eGFR. The use of calcium channel blockers [adjusted odds ratio (AOR): 0.70, 95% Confidence Interval (CI) 0.50-0.99] and the use of more than two antihypertensive medications (AOR: 0.62, 95% CI 0.40-0.96) were associated with reduced odds of optimal BP control. Male sex (AOR: 1.75, 95% CI 1.14-2.70) and the use of renin-angiotensin-aldosterone system blocking medications (AOR: 2.07, 95% CI 1.18-3.64) were independently associated with proteinuria while DM (AOR: 1.69, 95% CI 1.06-2.55) and treatment with more than two medications (AOR: 1.86, 95% CI 1.09-3.17) were more likely to have reduced eGFR.A large proportion of hypertensive patients in north-central Nigeria have poorly controlled BP. Kidney damage is common among these patients.

Dietary sodium intake and cardiovascular outcomes have a reported J-shaped curve relationship. This study analyzes the relationship between dietary sodium and sugar intake as a potential mechanism to explain this association. The authors examined cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2001-2016 where dietary sodium, carbohydrate, fat, cholesterol, and sugar intakes were assessed by 24-hour dietary recall and were standardized to a total daily intake of 2000 calories. Sodium intake was categorized into sodium quintiles (SQ) as follows: SQ1(0.06-2.6 g/d); SQ2(2.6-3.0 g/d); SQ3(3.0-3.4 g/d); SQ4(3.4-4.0 g/d); and SQ5(4.0-29.3 g/d). Simple and multivariate linear regression using SQ3 as reference were used to assess associations between daily sodium intake and the other nutrients. Our results showed that among 38 722 participants that met our study criteria, the mean age was 43.6 years (SD 16.8 years) and sex was equally distributed (48.8% male vs 51.2% female). Sugar intake went down across increasing SQs and was significantly higher in SQ1 (141.2 g/d) and SQ2 (118.6 g/d) and significantly lower in SQ4 (97.9 g/d) and SQ5 (85.6 g/d) compared to SQ3 (108.6 g/d; all P < .01). These same trends remained unchanged and significant in the fully adjusted multivariate model. In conclusion, NHANES study participants reporting low sodium intake on 24-hour dietary recall have a higher consumption of sugar. The negative impact of low sodium diet on cardiovascular health may be explained at least partially by the associated high sugar intake.

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.

The regulation of body fluid balance is a key concern in health and disease and comprises three concepts. The first concept pertains to the relationship between total body water (TBW) and total effective solute and is expressed in terms of the tonicity of the body fluids. Disturbances in tonicity are the main factor responsible for changes in cell volume, which can critically affect brain cell function and survival. Solutes distributed almost exclusively in the extracellular compartment (mainly sodium salts) and in the intracellular compartment (mainly potassium salts) contribute to tonicity, while solutes distributed in TBW have no effect on tonicity. The second body fluid balance concept relates to the regulation and measurement of abnormalities of sodium salt balance and extracellular volume. Estimation of extracellular volume is more complex and error prone than measurement of TBW. A key function of extracellular volume, which is defined as the effective arterial blood volume (EABV), is to ensure adequate perfusion of cells and organs. Other factors, including cardiac output, total and regional capacity of both arteries and veins, Starling forces in the capillaries, and gravity also affect the EABV. Collectively, these factors interact closely with extracellular volume and some of them undergo substantial changes in certain acute and chronic severe illnesses. Their changes result not only in extracellular volume expansion, but in the need for a larger extracellular volume compared with that of healthy individuals. Assessing extracellular volume in severe illness is challenging because the estimates of this volume by commonly used methods are prone to large errors in many illnesses. In addition, the optimal extracellular volume may vary from illness to illness, is only partially based on volume measurements by traditional methods, and has not been determined for each illness. Further research is needed to determine optimal extracellular volume levels in several illnesses. For these reasons, extracellular volume in severe illness merits a separate third concept of body fluid balance.

The development of formulas estimating glomerular filtration rate (eGFR) from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity, gender and age, has led to the current scheme of diagnosing and staging chronic kidney disease (CKD), which is based on eGFR values and albuminuria. This scheme has been applied extensively in various populations and has led to the current estimates of prevalence of CKD. In addition, this scheme is applied in clinical studies evaluating the risks of CKD and the efficacy of various interventions directed towards improving its course. Disagreements between creatinine-based and cystatin-based eGFR values and between eGFR values and measured GFR have been reported in various cohorts. These disagreements are the consequence of variations in the rate of production and in factors, other than GFR, affecting the rate of removal of creatinine and cystatin C. The disagreements create limitations for all eGFR formulas developed so far. The main limitations are low sensitivity in detecting early CKD in several subjects, e.g., those with hyperfiltration, and poor prediction of the course of CKD. Research efforts in CKD are currently directed towards identification of biomarkers that are better indices of GFR than the current biomarkers and, particularly, biomarkers of early renal tissue injury.

Aim To identify patients with end-stage renal disease treated by peritoneal dialysis (PD) who had zero body fat (BF) as determined by analysis of body composition using anthropometric formulas estimating body water (V) and to compare nutritional parameters between these patients and PD patients whose BF was above zero. Methods Body weight (W) consists of fat-free mass (FFM) and BF. Anthropometric formulas for calculating V allow the calculation of FFM as V/0.73, where 0.73 is the water fraction of FFM at normal hydration. Wasting from loss of BF has adverse survival outcomes in PD. Advanced wasting was defined as zero BF when V/0.73 is equal to or exceeds W. This study, which analyzed 439 PD patients at their first clearance study, used the Watson formulas estimating V to identify patients with VWatson/0.73 ≥ W and compared their nutritional indices with those of PD patients with VWatson/0.73 Results The study identified at the first clearance study two male patients with VWatson/0.73 ≥ W among 439 patients on PD. Compared to 260 other male patients on PD, the two subjects with advanced wasting had exceptionally low body mass index and serum albumin concentration. The first of the two subjects also had very low values for serum creatinine concentration and total (in urine and spent peritoneal dialysate) creatinine excretion rate while the second subject had an elevated serum creatinine concentration and high creatinine excretion rate due, most probably, to non-compliance with the PD prescription. Conclusion Advanced wasting (zero BF) in PD patients, identified by the anthropometric formulas that estimate V, while rare, is associated with indices of poor somatic and visceral nutrition.

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.

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. Review of published reports on DAH. Synthesis of guidelines based on these reports. 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. 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.

Since the beginning of life of the first multicellular organisms, the preservation of a physiologic milieu for every cell in the organism has been a critical requirement. A particular range of osmolality of the body fluids is essential for the maintenance of cell volume. In humans the stability of electrolyte concentrations and their resulting osmolality in the body fluids is the consequence of complex interactions between cell membrane functions, hormonal control, thirst, and controlled kidney excretion of fluid and solutes. Knowledge of these mechanisms, of the biochemical principles of osmolality, and of the relevant situations occurring in disease is of importance to every physician. This comprehensive review summarizes the major facts on osmolality, its relation to electrolytes and other solutes, and its relevance in physiology and in disease states with a focus on dialysis-related considerations.

Tumoral calcinosis (TC) is rare in patients with systemic sclerosis but is associated with morbidity. Paraspinal TC may cause severe pain and potentially devastating neurological deficits. Surgical decompression by removing the TC masses and applying surgical techniques to support the spine have provided substantial relief of the symptoms in the majority of cases. However, death has occurred in the immediate postoperative period and can even occur after several months. Current indications for surgery include intractable neck pain and, most importantly, the development of neurological deficits. We present a patient with systemic sclerosis and symptomatic paraspinal TC in the neck treated conservatively for two years. This case report illustrates conditions permitting the sustained conservative treatment of paraspinal TC in systemic sclerosis patients.

An anuric woman with ascites rapidly developed extreme hyperglycemia and seizures after hemodialysis. During development of hyperglycemia, the decrease in serum sodium concentration (Δ[Na]) was nearly twice the value predicted by a formula accounting for the degree of hyperglycemia and the intracellular-to-extracellular volume ratio. The prediction assumed that ascitic fluid is part of the extracellular volume. Potential contributors to the development of seizures include the rapid development of severe hypertonicity, a remote history of seizure disorder and development of dialysis disequilibrium syndrome. Observations in peritoneal dialysis suggest that fluid with sodium concentration lower than in the ascitic fluid is transferred from the abdominal cavity into the blood during rapid development of hyperglycemia. In this case, Δ[Na], which determines the tonicity level expected after correction of hyperglycemia, resulted from exit of both intracellular and ascitic fluid into the extracellular compartment and, therefore, ascitic fluid functions as an extension of the intracellular fluid.

A 77-year-old man on peritoneal dialysis (PD) presented repeatedly with cloudy spent dialysate containing an elevated mononuclear cell count. He had mantle cell lymphoma diagnosed by colonic polyp biopsy two years before the start of PD. The first episode of cloudy dialysate was treated for peritonitis. However, the culture of the peritoneal fluid was negative and the mononuclear cells were proven to be atypical lymphocytes of the mantle cell lymphoma variety. In addition to the peritoneal effluent, atypical lymphocytes were also found consistently in the patient's blood samples and once in his right pleural effusion. The patient exhibited high peritoneal transport status and clinical features of volume overload raising the question of alterations in the peritoneal transport processes in PD patients with malignancies involving the peritoneal membrane. Distinction between infectious and noninfectious cloudy dialysate and the potential of changes in the peritoneal membrane transport mechanisms are issues that should concern the care of PD patients with cloudy dialysate containing malignant cells.

An anuric peritoneal dialysis patient with diabetes mellitus, congestive heart failure, and anasarca developed severe hyperglycemia with hypertonicity causing profound neurological manifestations after prolonged and continuous use of hypertonic (4.25%) dextrose dialysate. She expired with hypotensive shock from a new myocardial infarction soon after completion of treatment with insulin infusion. The degree of the presenting hypertonicity far exceeded the value expected from the degree of hyperglycemia. We identified prolonged peritoneal dialysis with hypertonic solutions and profound extracellular volume expansion as the causes of the excessive hypertonicity. Hyperglycemia developing in diabetic patients treated for anasarca by peritoneal dialysis after continuous use of hypertonic dextrose dialysate is associated with the risk of excessive hypertonicity with severe clinical manifestations.

Although disturbances of serum tonicity (effective osmolality) may have dire consequences, only surrogate indices of tonicity are available in practice. This report identifies the appropriate index for expressing clinical states of dystonicity. Serum sodium concentration ([Na]S) and osmolality ([Osm]S) may be incongruent. When the tonicity state shown by [Osm]S is higher than [Na]S and the difference between the 2 indices is caused by an excess of solute that distributes in total body water, tonicity is described by [Na]S. When this difference results from a gain of solute with extracellular distribution like mannitol or a decrease in serum water content, causing a falsely low measurement of [Na]S, [Osm]S accurately reflects tonicity. Two indices of tonicity are applicable during hyperglycemia: the tonicity formula (2 ·[Na]S + [Glucose]S/18) and the corrected [Na]S ([Na]S corrected to a normal [Glucose]S using an empirically derived coefficient). Clinicians should understand the uses and limitations of the tonicity indices.

Hypertensive mechanisms are postulated to play a major role in the progressive glomerulosclerosis (GS) after renal mass reduction. But, in contrast to converting enzyme inhibitors, BP reduction by calcium channel blockers, has not provided consistent protection. Radiotelemetric BP monitoring for 7 wk was used to compare nifedipine (N) and enalapril (E) in the rat approximately 5/6 renal ablation model. After the first week, rats received N, E, or no treatment (C). The overall averaged systolic BP in C (173 +/- 7 mmHg) was reduced by both E and N (P < 0.001), but E was more effective (113 +/- 2 vs. 134 +/- 3 mmHg, P < 0.01). GS was prevented by E (2 +/- 1 vs. 26 +/- 5% in C) but not by N (25 +/- 6%). GS correlated well with the overall averaged BP in individual animals of all groups, but the slope of the relationship was significantly steeper in N compared with C+E rats (P < 0.02), suggesting greater pressure transmission to the glomeruli and GS for any given BP. Since autoregulatory mechanisms provide the primary protection against pressure transmission, renal autoregulation was examined at 3 wk in additional rats. Autoregulation was impaired in C rats, was not additionally altered by E, but was completely abolished by N. These data demonstrate the importance of autoregulatory mechanisms in the pathogenesis of hypertensive injury and suggest that calcium channel blockers which adversely affect pressure transmission may not provide protection despite significant BP reduction.

Osmotic diuresis results from urine loss of large amounts of solutes distributed either in total body water or in the extracellular compartment. Replacement solutions should reflect the volume and monovalent cation (sodium and potassium) content of the fluid lost. Whereas the volume of the solutions used to replace losses that occurred prior to the diagnosis of osmotic diuresis is guided by the clinical picture, the composition of these solutions is predicated on serum sodium concentration and urinary sodium and potassium concentrations at presentation. Water loss is relatively greater than the loss of sodium plus potassium leading to hypernatremia which is seen routinely when the solute responsible for osmotic diuresis (e.g., urea) is distributed in body water. Solutes distributed in the extracellular compartment (e.g., glucose or mannitol) cause, in addition to osmotic diuresis, fluid transfer from the intracellular into the extracellular compartment with concomitant dilution of serum sodium. Serum sodium concentration corrected to euglycemia should be substituted for actual serum sodium concentration when calculating the composition of the replacement solutions in hyperglycemic patients. While the patient is monitored during treatment, the calculation of the volume and composition of the replacement solutions for losses of water, sodium and potassium from ongoing osmotic diuresis should be based directly on measurements of urine volume and urine sodium and potassium concentrations and not by means of any predictive formulas. Monitoring of clinical status, serum sodium, potassium, glucose, other relevant laboratory values, urine volume, and urine sodium and potassium concentrations during treatment of severe osmotic diuresis is of critical importance.

Background The United States is faced with an unprecedented epidemic of drug abuse. Every year thousands of Americans visit the emergency departments all over the country with illicit drug related complaints. These drugs have been known to be associated with a range of renal pathologies, from reversible acute kidney injuries to debilitating irreversible conditions like renal infarction. So far, no comprehensive study or systematic review has been published that includes the commonly used street drugs and designer drugs with potential nephrotoxic outcomes. Methods We conducted a systematic review of published case reports, case series, and cross sectional studies of nephrotoxicities related to drugs of abuse. Literature review was conducted using PubMed/Medline from January 1, 2005 -December 31, 2016 to search for publications related to drug abuse with a defined renal outcome. Publications which reported renal injury in relation to the use of illicit drugs were selected, specifically those cases with raised creatinine levels, clinically symptomatic patients, for instance those with oliguria and proven renal biopsies. Results A total of 4798 publications were reviewed during the search process and PRISMA flow chart and Moose protocol regarding systematic reviews were followed. 110 articles were shortlisted for the review. A total of 169 cases from case reports and case series, and 14 case studies were analyzed. Renal manifestations of specific illicit drug abuse were included in this review. Conclusion Based on the evidence presented, a wide range of renal manifestations were found to be associated with drug abuse. If the trend of increasing use of illicit drug use continues, it will put a significant percentage of the population at an elevated risk for poor renal outcomes. This study is limited by the nature of the literature reviewed being primarily case reports and case series.

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.

Hypertonicity causes severe clinical manifestations and is associated with mortality and severe short-term and long-term neurological sequelae. The main clinical syndromes of hypertonicity are hypernatremia and hyperglycemia. Hypernatremia results from relative excess of body sodium over body water. Loss of water in excess of intake, gain of sodium salts in excess of losses or a combination of the two are the main mechanisms of hypernatremia. Hypernatremia can be hypervolemic, euvolemic or hypovolemic. The management of hypernatremia addresses both a quantitative replacement of water and, if present, sodium deficit, and correction of the underlying pathophysiologic process that led to hypernatremia. Hypertonicity in hyperglycemia has two components, solute gain secondary to glucose accumulation in the extracellular compartment and water loss through hyperglycemic osmotic diuresis in excess of the losses of sodium and potassium. Differentiating between these two components of hypertonicity has major therapeutic implications because the first component will be reversed simply by normalization of serum glucose concentration while the second component will require hypotonic fluid replacement. An estimate of the magnitude of the relative water deficit secondary to osmotic diuresis is obtained by the corrected sodium concentration, which represents a calculated value of the serum sodium concentration that would result from reduction of the serum glucose concentration to a normal level.

The precise cause of the antineutrophil cytoplasmic antibodies (ANCA) autoimmunity is not known and is likely to be multifactorial. Infections may trigger formation of ANCA and a fraction of the patients with infection-triggered ANCA develop ANCA-associated vasculitis. Here we discuss some of the proposed mechanisms of ANCA formation during the course of infection. They include initiation of autoimmune response by microbial peptides that are complementary to autoantigens; epigenetic silencing and antigen complementarity leading to upregulation of autoantigen genes; molecular mimicry between bacterial and self-antigens; formation of neutrophil extracellular traps that stimulate immune processes including production of ANCA; and interaction of bacterial components with Toll-like receptors, which leads to formation of mediators affecting the immune responses to infections and can trigger ANCA production. Further work is needed to clarify these mechanisms and develop preventive measures and therapeutic interventions.

Large differences between the concentrations of serum total carbon dioxide (TCO2) and blood gas bicarbonate (HCO3 (-)) were observed in two consecutive simultaneously drawn sets of samples of serum and arterial blood gases in a patient who presented with severe carbon dioxide retention and profound acidemia. These differences could not be explained by the effect of the high partial pressure of carbon dioxide on TCO2, by variations in the dissociation constant of the carbonic acid/bicarbonate system or by faults caused by the algorithms of the blood gas apparatus that calculate HCO3 (-). A recalculation using the Henderson-Hasselbach equation revealed arterial blood gas HCO3 (-) values close to the corresponding serum TCO2 values and clarified the diagnosis of the acid-base disorder, which had been placed in doubt by the large differences between the reported TCO2 and HCO3 (-) values. Human error in the calculation of HCO3 (-) was identified as the source of these differences. Recalculation of blood gas HCO3 (-) should be the first step in identifying the source of large differences between serum TCO2 and blood gas HCO3 (-).

This report attempts to frame the debate about clinical administration of sodium bicarbonate in the setting of lactic acidosis in terms of simple questions. Specifically, we address why we develop lactic acidosis in some circumstances, how acute lactic acidosis impairs cardiovascular function and why sodium bicarbonate may have deleterious effects which limit its utility. We also attempt to explore treatment alternatives to sodium bicarbonate.

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.

AIM To test whether muscle mass evaluated by creatinine excretion (EXCr) is maintained in patients with end-stage kidney disease (ESKD) treated by peritoneal dialysis (PD), we evaluated repeated measurements of EXCr in a PD population. METHODS One hundred and sixty-six PD patients (94 male, 72 female) receiving the same PD dose for the duration of the study (up to approximately 2.5 years) had repeated determinations of total (in urine plus spent dialysate) 24-h EXCr (EXCr T) to assess the adequacy of PD by creatinine clearance. All 166 patients had two EXCr T determinations, 84 of the 166 patients had three EXCr T determinations and 44 of the 166 patients had four EXCr T measurements. EXCr T values were compared using the paired t test in the patients who had two studies and by repeated measures ANOVA in those who were studied three or four times. RESULTS In patients who were studied twice, with the first and second EXCr T measurements performed at 9.2 ± 15.2 mo and 17.4 ± 15.8 mo after onset of PD, respectively, EXCr T did not differ between the first and second study. In patients studied three times and whose final assessment occurred 24.7 ± 16.3 mo after initiating PD, EXCr T did not differ between the first and second study, but was significantly lower in the third study compared to the first study. In patients who were studied four times and whose fourth measurement was taken 31.9 ± 16.8 mo after onset of PD, EXCr T did not differ between any of the studies. The average EXCr T value did not change significantly, with the exception of the third study in the patients studied thrice. However, repeated determinations of EXCr T in individuals showed substantial variability, with approximately 50% of the repeated determinations being higher or lower than the first determination by 15% or more. CONCLUSION The average value of EXCr T remains relatively constant for up to 2.5 years of follow-up in PD patients who adhere to the same PD schedule. However, repeated individual EXCr T values vary considerably in a large proportion of the patients. Further studies are needed to evaluate the clinical significance of varying EXCr T values and the stability of EXCr T beyond 2.5 years of PD follow-up.

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.