Ramesh Khanna

Vascular ossification – calcification in metabolic syndrome, type 2 diabetes mellitus, chronic kidney disease, and calciphylaxis – calcific uremic arteriolopathy: the emerging role of sodium thiosulfate

BackgroundVascular calcification is associated with metabolic syndrome, diabetes, hypertension, atherosclerosis, chronic kidney disease, and end stage renal disease. Each of the above contributes to an accelerated and premature demise primarily due to cardiovascular disease. The above conditions are associated with multiple metabolic toxicities resulting in an increase in reactive oxygen species to the arterial vessel wall, which results in a response to injury wound healing (remodeling). The endothelium seems to be at the very center of these disease processes, acting as the first line of defense against these multiple metabolic toxicities and the first to encounter their damaging effects to the arterial vessel wall.ResultsThe pathobiomolecular mechanisms of vascular calcification are presented in order to provide the clinician – researcher a database of knowledge to assist in the clinical management of these high-risk patients and examine newer therapies. Calciphylaxis is associated with medial arteriolar vascular calcification and results in ischemic subcutaneous necrosis with vulnerable skin ulcerations and high mortality. Recently, this clinical syndrome (once thought to be rare) is presenting with increasing frequency. Consequently, newer therapeutic modalities need to be explored. Intravenous sodium thiosulfate is currently used as an antidote for the treatment of cyanide poisioning and prevention of toxicities of cisplatin cancer therapies. It is used as a food and medicinal preservative and topically used as an antifungal medication.ConclusionA discussion of sodium thiosulfates dual role as a potent antioxidant and chelator of calcium is presented in order to better understand its role as an emerging novel therapy for the clinical syndrome of calciphylaxis and its complications.

Nephrogenic Systemic Fibrosis: A Mysterious Disease in Patients with Renal Failure—Role of Gadolinium-Based Contrast Media in Causation and the Beneficial Effect of Intravenous Sodium Thiosulfate

Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis (NSF) is an emerging scleromyxedema-like cutaneous disorder of unknown cause that is seen in patients with renal failure, and the number of reported cases has grown significantly since its first recognition. Recent case reports associated the use of gadolinium (Gd3+)-based contrast agents with the development of NSF. Herein is reported an additional patient who had NSF and had multiple previous exposures to Gd3+-based magnetic resonance imaging studies and had marked improvement in pain and skin changes after a trial of intravenous sodium thiosulfate. Discussed are the possible association of Gd3+-based contrast media with the development of NSF and potential for the use of sodium thiosulfate in the treatment of NSF.

Cross-sectional assessment of weekly urea and creatinine clearances in patients on continuous ambulatory peritoneal dialysis.

In 55 patients on continuous ambulatory peritoneal dialysis, the authors determined daily renal and dialysate clearances of urea nitrogen (CUN) and creatinine (CCr). Results are expressed as weekly CUN in liters (Kt) divided by liters of total body water determined from a nomogram (V). The authors calculated weekly CCr as the weekly dialysis clearance plus the average of renal CUN and CCr (to correct for creatinine secretion); they normalized total weekly CCr to 1.73 m2 body surface area. Mean weekly Kt/V and CCr were 2.1 and 65.2, respectively. Mean dietary protein intake by dietary survey was 0.85 g/kg body weight. Protein catabolic rate (PCR) calculated from urea kinetics was 0.94 g/kg standardized weight (V/0.58); PCR was significantly (p < 0.01) correlated with Kt/V (r = 0.53). The authors used linear regression to determine PCR, as follows: PCR = 0.80 [weekly Kt/V]/3 + 0.39. This slope is nearly 1.5 times that reported for the relationship of PCR to [weekly Kt/V]/3 in hemodialysis patients. Eighty-two percent of patients on continuous ambulatory peritoneal dialysis had more than the targeted minimum weekly Kt/V of 1.7, 71% had a weekly CCr more than the targeted minimum of 50, and 75% had a PCR > 0.8 g/kg/day. In support of the hypothesis that Kt/V requirements are related to peak concentration control rather than to time averaged blood urea nitrogen, patients on continuous ambulatory peritoneal dialysis have a higher PCR at given Kt/V values compared to hemodialysis patients. These patients are more likely to have a PCR > 0.8 if weekly Kt/V > 1.7.

Continuous Ambulatory Peritoneal Dialysis in Diabetics with End-Stage Renal Disease

Twenty diabetics with end-stage renal disease who had never previously received dialysis treatment were treated with continuous ambulatory peritoneal dialysis for periods of two to 36 months (average, 14.5). Intraperitoneal administration of insulin achieved good control of blood sugar. Even though creatinine clearance decreased significantly (P = 0.001), control of blood urea nitrogen and serum creatinine was adequate. Hemoglobin and serum albumin levels increased significantly (P = 0.005 and 0.04, respectively). Similarly, there was a significant increase in serum triglycerides and alkaline phosphatase (P = 0.02 and 0.05). Blood pressure became normal without medications in all but one of the patients. Retinopathy, neuropathy, and osteodystrophy remained unchanged. Peritonitis developed once in every 20.6 patient-months--a rate similar to that observed in nondiabetics. The calculated survival rate was 93 per cent at one year; the calculated rate of continuation on ambulatory peritoneal dialysis was 87 per cent. We conclude that continuous ambulatory dialysis with intraperitoneal administration of insulin is a good alternative treatment for diabetics with end-stage renal disease.

Intraabdominal Pressures during Natural Activities in Patients Treated with Continuous Ambulatory Peritoneal Dialysis

Intraabdominal pressures were measured during natural activities in 6 men, age 24-62 years, treated with continuous ambulatory peritoneal dialysis. The pressures were measured with a pressure transducer secured at the level of the umbilicus in the supine, sitting, and upright positions with 0-3 liters intraperitoneal fluid during talking, coughing, straining, changing position, walking, jogging, exercycling, jumping and weight lifting. Coughing and straining generated the highest intraabdominal pressures in every position. The pressures with weight lifting were proportional to the magnitude of the weight lifted up to 50 lbs, but were lower than those during coughing and straining. The pressures were generally higher with greater intraabdominal fluid volumes, especially with jumping and coughing. Exercycling was associated with lower intraabdominal pressure than was jogging, and the pressures were only minimally influenced by intraperitoneal fluid volumes. The results of this study can be used as a guide in establishing preventive measures in patients with intraperitoneal fluid to decrease complication rates related to raised intraabdominal pressures such as dialysate leaks, hernias and hemorrhoids.

Continuous ambulatory peritoneal dialysis with a high flux membrane

The standard peritoneal equilibration test (PET) was performed in 66 patients on CAPD. Patients were classified as low (n=5), low average (n=22), high average (n=27), and high (n=12) transporters based on the dialysate/plasma creatinine (D/P Cr) after 4 hour dwells. After an average time interval of 14 months on CAPD, indices of dialysis adequacy and nutrition were assessed. Based on monitoring of patient chemistries and drain volumes, peritoneal transport was considered stable during the interval. Instilled volumes and exchange tonicity were individualized in each patient to achieve combined renal and dialysis weekly creatinine clearance and KT/V urea that were not significantly different between groups. Overall, there were significant positive correlations of PET D/P Cr with dialysate albumin concentrations (r=0.30, p<0.02) and dialysate albumin losses (g/wk, r=0.27, p<0.04). There were significant inverse correlations with lean body mass (r=—0.26, p<0.03), drain volumes (r=—0.025, p<0.04), and KT urea by dialysis (L/wk, r=-0.24,p<0.05). High transporters had significantly (p<0.05) lower mean serum albumin, net protein catabolic rate (nPCR), lean body mass calculated from creatinine kinetics, and daily creatinine production (and presumably lower muscle mass) compared with one or more lower transport groups. In conclusion, we hypothesize that, in high transporters, use of more hypertonic exchanges with greater glucose absorption may inhibit appetite and nPCR; also, protein losses in drain volumes are increased. High transporters may require increased clearance and protein intake targets compared with other groups to maintain nutrition. Also, high transporters may be better suited for nightly intermittent peritoneal dialysis where short cycles provide more ultrafiltration with less glucose absorption.

The Relationship between Urine Osmolality and Specific Gravity

Background: In general, there is a good correlation between the specific gravity and osmolality of a urine sample. In certain clinical conditions, such as uncontrolled diabetes mellitus, nephrotic syndrome, after the administration of intravenous radiocontrast material or saline diuresis, dependence upon specific gravity for determining the concentrating ability will result in over‐ or underestimation. Methods: We studied the relationship between specific gravity and osmolality in vitro with simulated urines of varying composition. Urine samples from patients with different clinical conditions were also analyzed. Results: The in vitro curves for sodium chloride, urea, creatinine, glucose, contrast dye, and albumin were plotted (specific gravity versus osmolality). We found a linear correlation between the specific gravity and osmolality of the 6 substances that were studied and for their combinations. The urine samples obtained from patients with different clinical conditions documented that reliance on specific gravity could over‐ or underestimate the urine osmolality. Conclusions: We concluded that in those clinical conditions, urine osmolality should always be determined and it should not be estimated based on specific gravity.

Physiology of Peritoneal Dialysis

Adequate peritoneal dialysis maintains an end-stage renal disease patient symptom-free by partially replacing some of the functions performed by the healthy kidneys. Dialysis (a) removes solutes accumulated in the blood, such as urea nitrogen, creatinine. phosphate, potassium, water, etc., into the dialysis solution infused into the peritoneal cavity and (b) corrects acidosis by the addition of bicarbonate, by way of lactate, to the blood from the dialysis solution.

Peritonitis in Continuous Ambulatory Peritoneal Dialysis: Analysis of an 8-Year Experience

Experiences with peritonitis in a continuous ambulatory peritoneal dialysis (CAPD) program at a single center over 8 years were reviewed. Home-acquired peritonitis rates have been less than 1 episode per patient year since 1982. Gram-positive organisms continue to account for most episodes in a similar proportion. Actual known contamination could be pinpointed in only 7.4% of cases, but was strongly suspected in 35.8% of episodes. Exit site and/or tunnel infections were thought to have caused 20% of the cases. Intrinsic peritonitis probably accounted for 10.5%. Recurrence of peritonitis with the same organisms following cessation of antibiotics represented only 2.1% of cases.

Peritoneal Ultrafiltration for Chronic Congestive Heart Failure: Rationale, Evidence and Future

Peritoneal dialysis (PD) was the first dialytic therapy used to achieve euvolemia in individuals with refractory congestive heart failure. PD remains a viable therapy for the short-term management of refractory congestive heart failure, and fluid removal rates comparable to those obtained with the continuous extracorporeal therapies can be achieved. However, with advances in extracorporeal therapies, the role of PD in these situations is limited to those individuals in whom vascular access cannot be obtained or if extracorporeal therapies are not available. On the other hand, PD is the ultrafiltration therapy of choice for the long-term ambulatory management of individuals with refractory congestive heart failure, either as a palliative therapy or as a bridge to definitive surgery or transplantation. A reduction in hospitalization rates and an improvement in functional capacity can be expected under such circumstances; however, survival is unlikely to be affected.