Solute and Water Transport in Peritoneal Dialysis: A Case-Based Primer.

Peritoneal dialysis (PD) is an effective therapy for patients with end-stage kidney disease. Dialysis solutions containing physiologic concentrations of electrolytes and base, as well as glucose often at supraphysiologic concentrations, are infused into the peritoneal cavity for solute and water exchange, and the patient's own peritoneal membrane is used for dialysis. The peritoneal membrane is dominated by small pores, which allow transport of water and small-molecular-size solutes, including electrolytes, by way of both diffusion and convection. Through small pores, diffusion allows the movement of solutes from the high-concentration compartment to a lower-concentration region. Also, through small pores, water and solutes move together by convection in response to an osmotic force. The glucose in the dialysis solution generates osmotic force to drive convection. In addition to small pores, the peritoneal membrane contains a specialized water channel, aquaporin 1, which is also present in capillaries of the peritoneal membrane. These specialized water channels, which are upregulated by glucose, allow water transport without solute (free water) in response to the osmotic force induced by glucose in the PD solution. During a PD exchange, net loss or gain of electrolytes and base is determined by both their gradient between capillary blood and dialysis solution and the net ultrafiltration volume. Developing a PD prescription, including the amount of glucose used, and changing the prescription in response to dietary changes and/or loss of residual kidney function requires a sound understanding of the peritoneal physiology. The case studies presented here help solidify the basic elements of PD prescription and how the PD prescription should be altered in response to changing clinical situations.

Bleeding Peritoneum During Peritoneal Dialysis: A Case of Early Encapsulating Peritoneal Sclerosis?

Complications of peritoneal dialysis (PD) create a significant burden for patients and providers. Some complications, such as infections and leaks, are preventable or easily treatable; however, potential fatal complications, such as encapsulating peritoneal sclerosis (EPS), cost patients their lives. Here, we present the case of a PD patient who might have had early, subtle, but ominous symptoms and signs of EPS, diagnosed in its early stages and promptly managed.A 57-year-old man who had been receiving PD for 6 years began having recurrent episodes of abdominal pain, blood-tinged effluent, and peritonitis. Even after successful treatment of his peritonitis episode, his dialysate effluent would be intermittently hazy or pinkish. When he presented with similar complaints for the third time, he was diagnosed with EPS after laparoscopy for further evaluation during his hospitalization.Encapsulating peritoneal sclerosis is a rare complication of PD. The advanced stages of EPS with "EPS syndrome" portend a grave prognosis because of small-bowel obstruction, malnutrition, infection, and death. Early recognition and timely intervention can be a strategy to potentially prevent the progression of EPS.

Continuous Ambulatory Peritoneal Dialysis and Automated Peritoneal Dialysis: What, Who, Why, and How? Review and Case Study.

Peritoneal dialysis (PD) is an umbrella term that encompasses a variety of techniques such as continuous ambulatory PD, automated PD, tidal PD, and intermittent PD, among others. The various techniques exist to tailor the PD prescription to meet the goals of individual patients. Various clinical and nonclinical factors can change over time, requiring a change to the PD prescription. This article uses a practical case study to highlight the intricacies of the calculations behind PD prescription to achieve clearance goals. The objective is to demonstrate that all modalities of PD should be considered in the spectrum of clinical tools for achieving adequate dialysis.

Diagnostic Dilemma: A Case of Endogenous Peritonitis.

Endogenous peritonitis resulting from inflammation or perforation of an abdominal viscus-a result, for example, of diverticulitis, cholecystitis, or acute appendicitis-can be a complication in patients undergoing peritoneal dialysis (PD), with significant morbidity and a high incidence of catheter loss.Here, we describe an end-stage renal disease patient on PD who presented with acute abdominal pain and who was diagnosed with uncomplicated PD peritonitis. His clinical course was complicated by development of eosinophilic peritonitis because of an allergy to vancomycin. Subsequently, when he failed to show clinical improvement, abdominal and pelvic imaging revealed severe appendicitis, which necessitated emergent surgical intervention.

Nanotechnology and adeno-associated virus-based decorin gene therapy ameliorates peritoneal fibrosis.

Peritoneal dialysis (PD) is a life-sustaining therapy for end-stage renal disease (ESRD), used by 10-15% of the dialysis population worldwide. Peritoneal fibrosis (PF) is a known complication of long-term PD and frequently follows episodes of peritonitis, rendering the peritoneal membrane inadequate for dialysis. Transforming growth factor (TGF)-ß is an inducer of fibrosis in several tissues and organs, and its overexpression has been correlated with PF. Animal models of peritonitis have shown an increase in expression of TGF-ß in the peritoneal tissue. Decorin, a proteoglycan and component of the extracellular matrix, inactivates TGF-ß, consequently reducing fibrosis in many tissues. Recently, gold nanoparticles (GNP) have been used for drug delivery in a variety of settings. In the present study, we tested the possibility that GNP-delivered decorin gene therapy ameliorates zymosan-mediated PF. We created a PF model using zymosan-induced peritonitis. Rats were treated with no decorin, GNP-decorin, or adeno-associated virus-decorin (AAV-decorin) and compared with controls. Tissue samples were then stained for Masson's trichrome, enface silver, and hematoxylin and eosin, and immunohistochemistry was carried out with antibodies to TGF-ß1, α-smooth muscle actin (α-SMA), and VEGF. Animals which were treated with GNP-decorin and AAV-decorin gene therapy had significant reductions in PF compared with untreated animals. Compared with untreated animals, the treated animals had better preserved peritoneal mesothelial cell size, a significant decrease in peritoneal thickness, and decreased α-SMA. Quantitative PCR measurements showed a significant decrease in the peritoneal tissue levels of α-SMA, TGF-ß, and VEGF in treated vs. untreated animals. This study shows that both GNP-delivered and AAV-mediated decorin gene therapies significantly decrease PF in vivo in a rodent model. This approach has important clinical translational potential in providing a therapeutic strategy to prevent PF in PD patients.

Peritoneal dialysis peritonitis: common presentation by an uncommon organism.

Peritonitis remains a leading complication of peritoneal dialysis (PD). About 18% of the infection-related mortality in PD patients is a result of peritonitis. We present a case of peritonitis in a patient on automated PD in whom the infection was not related to a break in PD technique, but to an unusual cause: retrograde transmission of a gonococcal organism.

Post-transplant Lymphoproliferative Disorder--a case of late-onset T-cell lymphoma after failed renal transplant.

Post-transplant lymphoproliferative disease (PTLD) is a rare but life-threatening complication after solid organ transplantation. The risk of PTLD varies with recipient age, serostatus of the donor and the recipient for Epstein-Barr virus, type of organ transplanted, and intensity of immunosuppression. The risk of PTLD is highest in the early post-transplant period, but the cumulative risk increases with time. We report a case of PTLD occurring 17 years after renal transplantation in a 59-year-old woman.

Clinical presentation & management of glomerular diseases: hematuria, nephritic & nephrotic syndrome.

Because the differential diagnosis for glomerulonephritis (GN) is broad, using a classification schema is helpful to narrow the causes of GN in a systematic manner. The etiology of glomerulonephritis can be classified by their clinical presentation (nephrotic, nephritic, rapidly progressive GN, chronic GN) or by histopathology. GN may be restricted to the kidney (primary glomerulonephritis) or be a secondary to a systemic disease (secondary glomerulonephritis). The nephrotic syndrome is defined by the presence of heavy proteinuria (protein excretion greater than 3.0 g/24 hours), hypoalbuminemia (less than 3.0 g/dL), and peripheral edema. Hyperlipidemia and thrombotic disease may be present. The nephritic syndrome is associated with hematuria and proteinuria and abnormal kidney function and carries poorer prognosis and is typically associated with hypertension. The predominant cause of the nephrotic syndrome in children is minimal change disease. The most common causes of nephritic syndrome are post infectious GN, IgA nephropathy and lupus nephritis. Chronic GN is slowly progressive and is associated with hypertension and gradual loss of kidney function. Treatment includes non-specific measure aimed at controlling hypertension, edema, proteinuria and disease modifying immunosuppression.

Renal replacement therapies.

The kidneys perform a wide array of functions in the body, most of which are essential for life. Regulation of water and electrolytes, excretion of metabolic waste and of bioactive substances like hormones, drugs etc., which affect bodily functions; regulation of arterial blood pressure, red blood cell and vitamin D production; are some of the major functions that the kidneys perform. It is obvious then, that patients with renal failure present a steep challenge to the physician taking care of this special population. Renal replacement therapy remains only a part of treatment that helps substitute the regulation of water and electrolytes, removal of metabolic waste, and to a certain extent removal of drugs and other bioactive substances from the body. This article aims to provide an understanding of different types of renal replacement therapy, mainly to patients with end-stage renal disease (ESRD).

Renal replacement therapy in end-stage renal disease patients with chronic liver disease and ascites: role of peritoneal dialysis.

Chronic liver disease and cirrhosis account for several thousand deaths in the United States and often these patients have renal disease that progresses to end-stage renal disease (ESRD), necessitating renal replacement therapy. These patients provide significant challenges to their physicians, especially in the management of their ESRD with dialysis. ESRD patients with chronic liver disease and ascites are more difficult to manage on hemodialysis (HD) due to their hemodynamic status and risk of bleeding. Peritoneal dialysis (PD) offers them a viable alternative, along with a stable hemodynamic status and a lower risk of bleeding. The overall morbidity and mortality as well as the risk of peritonitis appear to be almost similar between cirrhotic and non-cirrhotic PD patients. In the absence of clinical trials comparing HD versus PD in such a population, and despite the limited clinical observations, the authors support PD as a viable and effective form of renal replacement therapy for patients with ESRD and associated chronic liver disease with cirrhosis and ascites.

A series of unusual complications of the presternal peritoneal dialysis catheter.

An ongoing problem for peritoneal dialysis (PD) patients has been complications associated with an indwelling PD catheter. The indwelling catheter has been through many modifications aimed at reducing complications and providing effective delivery of dialysis solution. In this report, we review four cases of rare complications associated with presternal PD catheters and a brief review of the Tenckhoff, Toronto Western Hospital, and Missouri swan-neck abdominal and presternal PD catheters.

Calciphylaxis: calcific uremic arteriolopathy and the emerging role of sodium thiosulfate.

Calciphylaxis-calcific uremic arteriolopathy, is a serious disorder of arteriolar calcification of the arteriole media and is associated with endovascular fibrosis and thrombosis in subcutaneous adipose tissue. It frequently results in severe ischemia, intense pain, and tissue necrosis with nonhealing skin ulcerations. It usually occurs in chronic kidney disease and especially in patients requiring renal replacement therapy. It is associated with a very high mortality rate, and the number of reports and reviews seemed to have increased over the past 5 years. Advances in therapy and salvaging patients from this high mortality risk have recently been reported with the use of sodium thiosulfate. The new application for this old drug used to treat cyanide poisoning and recently preventing neurotoxic effects resulting in hearing loss in those patients with head and neck cancer receiving cisplatin and carboplatin therapy are discussed. Recently, multiple case reports have demonstrated that sodium thiosulfate therapy has resulted in rapid pain relief, healing of skin ulcerations, and prevention of high mortality risk. This emerging treatment and its success are relatively unknown to many physicians. The purpose of this report is to share with others the emerging role of sodium thiosulfate and its new application as a treatment option to be used in combination with other treatment modalities for calciphylaxis-calcific uremic arteriolopathy. Indeed, as with any new treatment this emerging therapy should be studied in greater detail, but this old drug seems to have a new life in the hands of treating physicians.

Predictors of hospitalization in patients on peritoneal dialysis: the Missouri experience.

BACKGROUND: We analyzed a large number of demographic and biochemical variables to identify predictors of hospitalization in subjects on peritoneal dialysis (PD). METHODS: All patients initiated on PD at our center from January 1990 through December 1999 were included. The following variables at the initiation of PD were included: demographics, clinical data, nutritional and adequacy parameters, transport characteristics, and various co-morbidities. Co-morbidities were graded for severity using a modified version of the Index of Coexistent Disease. Variables included during the course of PD consisted of weighted time average of a number of laboratory, adequacy, and nutritional parameters along with the number of peritonitis episodes per year. Stepwise linear regression was used following a univariate screening procedure to identify independent predictors of the outcome of hospitalization days per month on PD. RESULTS: The subject population consisted of 191 subjects (105 men, 86 women; 180 Caucasians, 10 African-American, 1 Asian). The mean age was 61 +/- 13 (SD) years and mean duration of follow-up was 21 +/- 18 months. The baseline variable analysis revealed that the presence of partner to perform PD predicted increased hospitalization (p < 0.0001). Additionally, the presence and severity of peripheral vascular disease and residual renal Kt/V at baseline (negative association) predicted increased hospitalization. In the analyses of ongoing variables, stepwise linear regression solely identified weighted time average albumin as a strong negative predictor of hospitalization (p < 0.0001). CONCLUSION: A comprehensive analysis of a large number of variables revealed that serum albumin during the course of PD (negative association) and the need for partner to perform PD strongly predicted increased hospitalization in PD subjects.

Peritoneal dialysis or hemodialysis? A dilemma for the nephrologist.

Selection of the initial dialysis modality is crucial in the treatment of end-stage renal disease (ESRD) patients. Several patient- and physician-related factors play important roles in the decision between peritoneal dialysis (PD) and hemodialysis (HD). Although HD is the most common dialysis modality in the United States, in some studies PD has shown a survival advantage over HD, at least in the first 2 years of dialysis treatment, especially in non-diabetic patients and in young patients with diabetes. Other advantages accrue to early PD use in many patients. An integrated care approach with "healthy start" and PD as the initial renal replacement therapy, followed by timely transfer to HD once complications arise, may improve the long-term survival of ESRD patients.

Detecting microalbuminuria and taking action in the cardiometabolic syndrome and type 2 diabetes mellitus.

Microalbuminuria is an early indicator of cardiac and renal vascular endothelial damage in individuals with diabetes mellitus, impaired glucose tolerance, hypertension, and the CardioMetabolic Syndrome. This simple, inexpensive dipstick screening test is not only associated with an increased risk of progressive renal insufficiency but also with an increased risk of cardiovascular disease and events. Regular screening for microalbuminuria will allow for early detection and intervention to prevent renal and vascular complications of these disease states.

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

BACKGROUND: Vascular 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. RESULTS: The 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 poisoning and prevention of toxicities of cisplatin cancer therapies. It is used as a food and medicinal preservative and topically used as an antifungal medication. CONCLUSION: A discussion of sodium thiosulfate's 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.