Establishing the presence or absence of chronic kidney disease:Uses and limitations of formulas estimating the glomerular filtration rate

The development of formulas estimating glomerular filtration rate(eG FR) 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 e GFR 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 e GFR values and between e GFR 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 e GFR 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.

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 m Osm/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 newonset 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.

Nephropathy in dietary hyperoxaluria:A potentially preventable acute or chronic kidney disease

Hyperoxaluria can cause not only nephrolithiasis and nephrocalcinosis,but also renal parenchymal disease histologically characterized by deposition of calcium oxalate crystals throughout the renal parenchyma,profound tubular damage and interstitial inflammation and fibrosis.Hyperoxaluric nephropathy presents clinically as acute or chronic renal failure that may progress to endstage renal disease(ESRD).This sequence of events,well recognized in the past in primary and enteric hyperoxalurias,has also been documented in a few cases of dietary hyperoxaluria.Estimates of oxalate intake in patients with chronic dietary hyperoxaluria who developed chronic kidney disease or ESRD were comparable to the reported average oxalate content of the diets of certain populations worldwide,thus raising the question whether dietary hyperoxaluria is a primary cause of ESRD in these regions.Studies addressing this question have the potential of improving population health and should be undertaken,alongside ongoing studies which are yielding fresh insights into the mechanisms of intestinal absorption and renal excretion of oxalate,and into the mechanisms of development of oxalate-induced renal parenchymal disease.Novel preventive and therapeutic strategies for treating all types of hyperoxaluria are expected to develop from these studies.

Hypertonicity:Clinical entities,manifestations and treatment

Hypertonicity causes severe clinical manifestations and is associated with mortality and severe short-term and longterm 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.

Respiratory failure in diabetic ketoacidosis

Respiratory failure complicating the course of diabetic ketoacidosis(DKA)is a source of increased morbidity and mortality.Detection of respiratory failure in DKA requires focused clinical monitoring,careful interpretation of arterial blood gases,and investigation for conditions that can affect adversely the respiration.Conditions that compromise respiratory function caused by DKA can be detected at presentation but are usually more prevalent during treatment.These conditions include deficits of potassium,magnesium and phosphate and hydrostatic or non-hydrostatic pulmonary edema.Conditions not caused by DKA that can worsen respiratory function under the added stress of DKA include infections of the respiratory system,pre-existing respiratory or neuromuscular disease and miscellaneous other conditions.Prompt recognition and management of the conditions that can lead to respiratory failure in DKA may prevent respiratory failure and improve mortality from DKA.

Fluid balance concepts in medicine:Principles and practice

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.

Advanced wasting in peritoneal dialysis patients

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) andBF.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 V_(Watson)/0.73 ≥ W and compared their nutritional indices with those of PD patients with V_(Watson)/0.73 < W.RESULTS The study identified at the first clearance study two male patients with V_(Watson)/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.

Reproducibility of serial creatinine excretion measurements in peritoneal dialysis

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.