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End stage renal disease (ESRD) is the final step in kidney failure. The skin may be the first clue to the disease.

Signs and Symptoms
Skin color changes (Pallor, Sallow, yellowish cast, Hyperpigmentation)
Xerosis, poor skin turgor, acquired ichthyosis
Uremic frost
Half-and-half nails

Specific disorders
Perforating disorders
Metastatic calcification
Benign nodular calcification
Bullous dermatosis
Nephrogenic Fibrosing Dermopathy
Porphyria cutanea tarda


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Gross Appearance and Clinical Variants  
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Management of early chronic kidney disease in indigenous populations and ethnic minorities.

Nicholas SB, Tareen N, Zadshir A, Martins D, Pan D, Norris KC.

David Geffen School of Medicine at University of California; and Charles R. Drew University of Medicine & Science, Los Angeles, California.

Kidney Int Suppl. 2005 Aug;(97):S78-81. Abstract quote  

Management of early chronic kidney disease in indigenous populations and ethnic minorities. The rate of treated end-stage renal disease (ESRD) continues to increase globally. The disproportionately high rate of ESRD among the many growing indigenous populations and racial/ethnic minorities in the United States highlights the need to reassess present treatment strategies to more appropriately identify and manage chronic kidney disease in diverse communities. Similar projections have been noted worldwide.

This discrepancy between ESRD rates among racial and ethnic minority groups, and treatment strategies is due to several factors, many of which are modifiable. These include the individual, the health care provider/system, and limited participation in controlled clinical trials.

Although it is unfortunate that this disparity continues to exist, a thoughtful and compassionate approach to addressing the role of diverse biobehavioral and sociocultural factors might be the key to effective translation of emerging scientific advances into improved clinical outcomes for all patients with chronic kidney disease.



Prevalence and characterization of uremic pruritus in patients undergoing hemodialysis: Uremic pruritus is still a major problem for patients with end-stage renal disease.

Zucker I, Yosipovitch G, David M, Gafter U, Boner G.

J Am Acad Dermatol. 2003 Nov;49(5):842-6. Abstract quote  

BACKGROUND: Pruritus is a common disabling problem in patients with advanced end-stage renal disease. Few studies have evaluated the clinical characteristics of uremic itch.

OBJECTIVES: The aim of this multicenter study was to provide a comprehensive description of the prevalence and clinical characteristics of pruritus affecting patients with end-stage renal disease who are undergoing hemodialysis.

METHODS: A detailed questionnaire recently developed was used to evaluate pruritus in 219 patients undergoing hemodialysis treatment in 3 dialysis units. We examined the relationship of the quality of dialysis and various factors and medical parameters to itch.

RESULTS: Pruritus was a common symptom in the study population. Approximately 66% of the patients had pruritus at some point, and 48% were affected by it at the time of the study. There was no correlation between the occurrence of pruritus and demographic or medical parameters (type of kidney disease, medical management, dialysis efficacy as expressed by Kt/V) of the patient. The data suggest that uremic pruritus tends to be prolonged, frequent, and intense, and it can impair the patient's quality of life including a negative effect on sleep and mood. Major factors found to exacerbate pruritus include rest, heat, dry skin, and sweat. Major factors found to reduce pruritus include activity, sleep, hot and cold shower, and cold. Treatment with angiotensin inhibitors seemed to be more common among those with uremia who had itch (P =.02) whereas furosemide was more commonly used among those who never itched (P =.002).

CONCLUSION: This study provides a detailed description of uremic pruritus with new data on its characteristics including affective and sensory dimensions and associated symptoms.



Expression of matrix metalloproteinase in the fluids of renal cystic lesions.

Harada H, Furuya M, Ishikura H, Shindo J, Koyanagi T, Yoshiki T.

Division of Pathophysiological Science, Department of Pathology/Pathophysiology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

J Urol 2002 Jul;168(1):19-22 Abstract quote

PURPOSE: Cystic lesions of the kidney are common conditions usually diagnosed by imaging. Although simple cysts are easy to diagnose, preoperative diagnosis of a complicated cystic lesion can be difficult. There is little information available on the biological activity of cystic fluid and associations with clinicopathological findings. We analyzed the expression of matrix metalloproteinase (MMP) in the fluids of benign and malignant renal cystic lesions to clarify matriolytic activities in the cyst.

MATERIALS AND METHODS: Included in this study were 22 samples of cystic fluids from renal cystic lesions, including 14 benign cysts and 8 cystic renal cell carcinomas. MMP-2 and 9 was determined in fluids using gelatin zymography and enzyme-linked immunosorbent assay.

RESULTS: MMP-2 expression was ubiquitously observed on zymography except for 2 benign cysts associated with acquired cystic disease of the kidney. MMP-9 was detected in 7 of 8 carcinomas but in only 2 of 14 benign cysts (p <0.01). The concentration of MMP-2 and 9 was significantly higher in cystic carcinomas than in benign cysts (p <0.01).

CONCLUSIONS: Our data show that MMPs were detectable in cystic fluids in the presence of renal cystic changes. MMP-2 and 9 are more abundant in cystic carcinoma fluids than in benign cystic fluids. These observations suggest that matriolytic enzymes in renal cystic fluid reflect biological aggressiveness and in part explain the pathogenesis of renal cystic lesions.

Atypical epithelial proliferations in acquired renal cystic disease harbor cytogenetic aberrations.

Cheuk W, Lo ES, Chan AK, Chan JK.

Department of Pathology, Queen Elizabeth Hospital, Kowloon, Hong Kong, SAR China.

Hum Pathol 2002 Jul;33(7):761-5 Abstract quote

Acquired renal cystic disease (ARCD) complicating end-stage renal failure confers an increased risk for renal cell carcinoma, and atypical epithelial proliferation in the cysts may represent the precursor lesion.

In this report we used an interphase cytogenetic technique to analyze the karyotypic features of various forms of atypical epithelial proliferations in a patient with ARCD. Both kidneys harbored numerous simple and atypical cysts. In addition, papillary tufts and a hitherto undescribed cribriform epithelial proliferation were found in the right kidney. The left kidney contained a 10-mm renal cell carcinoma with features indeterminate between clear cell and papillary types. There was gain of chromosome 7 in the papillary tufts; gain of chromosomes 7 and 17 in the cribriform lesion; gain of chromosomes 7, 12, 17, 20, and Y in the atypical cysts; and gain of chromosomes 7, 12, 17, and 20 in the renal cell carcinoma.

These chromosomal aberrations suggest that atypical epithelial proliferations in ARCD represent early neoplastic lesions.

Highly Active Antiretroviral Therapy and the Epidemic of HIV+ End-Stage Renal Disease.

Schwartz EJ, Szczech LA, Ross MJ, Klotman ME, Winston JA, Klotman PE.
J Am Soc Nephrol. 2005 Aug;16(8):2412-20. Epub 2005 Jun 29. Abstract quote  

The rise in the number of patients with HIV-associated nephropathy and HIV-infection with end-stage renal disease (HIV+ ESRD) continues to be a substantial concern for the ESRD program.

In order to assess the impact of highly active antiretroviral therapy (HAART) on the progression of patients with AIDS to the development of ESRD and to project the prevalence of HIV+ ESRD through 2020, a mathematical model of the dynamics of HIV+ infection in the ESRD population was developed. Epidemiologic data on AIDS and HIV+ ESRD among black individuals in the United States were obtained since 1991 from the Centers for Disease Control and Prevention and US Renal Data System, respectively. The model was constructed to predict the prevalence of HIV+ ESRD incorporating the current rate of growth in AIDS prevalence. Two possible trends were considered: linear AIDS growth and exponential AIDS growth. The likely effectiveness of HAART in slowing progression to HIV+ ESRD was estimated from the best fit of the model to the data after 1995, when HAART was introduced. The model was then used to evaluate recent data and to project the prevalence of HIV+ ESRD through 2020. The model suggested that HAART has reduced the rate of progression from AIDS to HIV+ ESRD by 38%. The model projected an increase in HIV+ ESRD prevalence in the future as a result of the increase in the AIDS population among black individuals.

This increase was predicted even assuming a 95% reduction in the progression from AIDS to HIV+ ESRD. Despite the potential benefit of HAART, the prevalence of HIV+ ESRD in the United States is expected to rise in the future as a result of the expansion of the AIDS population among black individuals. It is concluded that prevention of progression to ESRD should focus on early antiretroviral treatment of HIV-infected patients who have evidence of HIV-associated nephropathy.


Spectrum of Epithelial Neoplasms in End-Stage Renal Disease: An Experience From 66 Tumor-Bearing Kidneys With Emphasis on Histologic Patterns Distinct From Those in Sporadic Adult Renal Neoplasia.

Tickoo SK, Deperalta-Venturina MN, Harik LR, Worcester HD, Salama ME, Young AN, Moch H, Amin MB.

From the Departments of Pathology, *Memorial Sloan-Kettering Cancer Center, New York, NY; daggerWilliam Beaumont Hospital, Royal Oak, MI; double daggerHenry Ford Hospital Detroit, MI; section signEmory University Medical Center, Atlanta, GA; and parallelUniversity of Zurich, Zurich, Switzerland.

Am J Surg Pathol. 2006 Feb;30(2):141-153. Abstract quote  

Most (up to 71%) of renal cell neoplasms occurring in patients with end-stage renal disease (ESRD), particularly with acquired cystic disease of the kidney (ACDK), have been reported to be papillary renal cell carcinoma (RCC).

Our initial experience with tumors in such a setting indicated that many tumors were histologically difficult to classify into the known subtypes of RCC or had features that were different from those in sporadically occurring RCCs. In this study on 66 ESRD kidneys (52 of which showed features of ACDK) removed because tumors were detected in them, we found two major groups of RCC. Overall, there were 261 grossly identified tumors in these kidneys, and many additional tumors were observed on microscopic evaluation in some. Of the two major groups of RCCs, one consisted of tumors similar to those seen in sporadic settings (ie, clear-cell, papillary, and chromophobe RCC), and these formed the dominant mass in 12 (18%), 10 (15%), and 5 (8%) of the 66 kidneys, respectively. The other group consisted of two subtypes of RCC that appear quite unique to ESRD. The more common tumor that we have designated as "acquired cystic disease-associated RCC" was seen as the dominant mass in 24 (36%) of 66 of the kidneys, and it formed the most common tumor type among the smaller nondominant masses, as well. It was characterized by a typical microcystic architecture, eosinophilic cytoplasm with Fuhrman's grade 3 nuclei, and frequent association with intratumoral oxalate crystals. Additionally, these tumors frequently, but usually focally, exhibited papillary architecture, and clear cytoplasm. These tumors occurred only in kidneys with ACDK, and not in noncystic ESRD. The other category was "clear-cell papillary RCC of the end-stage kidneys," present as the dominant mass in 15 (23%) of the 66 kidneys and occurring in both the ACDK and noncystic ESRD. These predominantly cystic tumors showed prominent papillary architecture with purely clear-cell cytology.

Immunohistochemical studies in tumors with histology similar to the known subtypes of sporadic RCC showed immunoprofiles similar to that reported in sporadically occurring tumors. The two subtypes of RCC unique to ESRD had distinctive immunoprofiles supporting their separate morphologic subcategorization. Only the acquired cystic disease-associated RCC showed lymph node metastases in 2 cases and sarcomatoid features in 2 more cases. One of the latter 2 died with widespread metastatic disease within 34 months of nephrectomy. Thus, a broad spectrum of renal cell tumors exist in ESRD, only some of which resemble the sporadic RCCs.

Acquired cystic disease-associated RCC is the commonest tumor subtype in ESRD, and biologically it appears to be more aggressive than the other tumor subtypes in ESRD.


Cardiovascular disease as a late complication of end-stage renal disease in children.

Groothoff J, Gruppen M, de Groot E, Offringa M.

Department of Pediatric Nephrology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands.
Perit Dial Int. 2005 Feb;25 Suppl 3:S123-6. Abstract quote  

OBJECTIVE: To analyze the late cardiovascular outcome of end-stage renal disease (ESRD) in children.

DESIGN: A nation-wide long-term follow-up study. Determinants of outcomes and causes of death were retrospectively assessed. Patients underwent assessment of overall health state, B- and M-mode ultrasound of the carotid arteries, and echocardiography for cross-sectional analysis.

RESULTS: We analyzed the medical course of all 249 adult Dutch patients with ESRD onset between 1972 and 1992 at age 0 - 14 years, and who were born before 1979. Of the 187 living patients, 140 participated in the cross-sectional part of the study. The standardized mortality rate was 31.0. Overall 5-, 10-, and 20-year survival after ESRD onset was 87%, 82%, and 78%, respectively. Cardiovascular disease accounted for most deaths (41%). In the whole group, left ventricular hypertrophy (LVH), aortic valve calcification, and arterial wall stiffening were highly prevalent. LVH was associated with hypertension at time of assessment. Aortic valve calcification was strongly associated with a long total duration of peritoneal dialysis (beta = 0.33, p < 0.001). Arterial wall pathology was not associated with current treatment modality.

CONCLUSIONS: As in adults, cardiovascular disease is the most important cause of death in children with ESRD. Stricter reduction of volume overload, prevention of high serum calcium-phosphate product, and more vigorous treatment of hypertension are important targets to improve cardiovascular survival in children with ESRD.
Cardiovascular morbidity and mortality in children with chronic kidney disease in North America: lessons from the USRDS and NAPRTCS databases.

Mitsnefes MM.

Division of NephroLogy and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Perit Dial Int. 2005 Feb;25 Suppl 3:S120-2. Abstract quote  

Cardiovascular (CV) disease mortality has not changed in the past three decades, remaining the second most common cause of death in children with end-stage renal disease (ESRD). This article reviews pediatric data pertaining to CV disease obtained from the two largest renal databases in North America.

The data indicate high incidence and prevalence of CV complications and cardiac risk factors in children with ESRD, accounting for high cardiac mortality in this patient population.

Early identification and intervention to treat modifiable risk factors and asymptomatic cardiac disease might lead to prevention of cardiac disease and to a decrease in CV morbidity and mortality in young adults who developed chronic kidney disease during childhood.
Once-weekly intravenous paricalcitol in the treatment of secondary hyperparathyroidism in hemodialysis patients.

Staniforth ME, Cheng SC, Coyne DW.

Department of Internal Medicine, Renal Division, Washington University School of Medicine, St. Louis, MO 63110, USA.
Clin Nephrol. 2005 Jun;63(6):454-60. Abstract quote  

BACKGROUND: Paricalcitol, a vitamin D analog, is commonly administered three times weekly to control secondary hyperparathyroidism in hemodialysis patients. Less frequent dosing would be more convenient, require less nursing time, and be an option in other dialysis modalities. No studies have examined the efficacy of once-weekly dosing of paricalcitol.

METHODS: Chronic hemodialysis patients receiving a stable dose of paricalcitol three times weekly with intact PTH (iPTH) 100-500 ng/l were monitored during a two-week baseline, then were converted to a single mid-week paricalcitol dose equal to the previous cumulative weekly dose. Serum calcium and phosphorus were monitored weekly and iPTH levels determined during study Weeks 4 and 8. A single paricalcitol dose adjustment was made during study Week 5 based on iPTH to achieve a target value of 150-300 ng/l. Phosphate binders and calcium dialysate bath were kept constant during the study.

RESULTS: In the 25 patients, mean iPTH was 295 +/- 107 ng/l at baseline, and not significantly different at Week 4 (307 +/- 111 ng/l) or Week 8 (285 +/- 98 ng/l). Paricalcitol dose increases mid-study were almost exclusively in patients with iPTH > 300 ng/l. Calcium, phosphorus, and calcium x phosphorus product were not significantly different on weekly therapy. (Only one patient developed a calcium > 2.55 mmol/l during the study.)

CONCLUSION: Once-weekly dosing of paricalcitol is an effective option in treatment of secondary hyperparathyroidism. Less frequent dosing may better allocate nursing time and potentially benefit other patient populations with CKD and ESRD.
Treatment of osteoporosis in chronic kidney disease and end-stage renal disease.

Miller PD.

Colorado Center for Bone Research, 3190 South Wadsworth #250, Lakewood, CO 80227, USA.
Curr Osteoporos Rep. 2005 Mar;3(1):5-12. Abstract quote  

As glomerular filtration rate (GFR) declines from age-related bone loss or disease that specifically induces a decline in GFR, there are a number of metabolic bone conditions that may accompany the decline in GFR.

These metabolic bone conditions span a spectrum from mild-to-severe secondary hyperparathyroidism in early stages of chronic kidney disease (CKD) to the development of additional heterogeneous forms of bone diseases each with its distinctly quantitative bone histomorphometric characteristics. Osteoporosis can also develop in patients with CKD and ESRD for many reasons beyond age-related bone loss and postmenopausal bone loss.

The diagnosis of osteoporosis in patients with severe CKD or end-stage renal disease (ESRD) is not as easy to do as it is in patients with postmenopausal osteoporosis (PMO)--neither fragility fractures nor The World Health Organization bone mineral density criteria can be used to diagnose osteoporosis in this population since all forms of renal bone disease may fracture or have low "T scores". The diagnosis of osteoporosis in patients with CKD/ESRD must be done by first the exclusion of the other forms of renal osteodystrophy, by biochemical profiling or by double tetracycline-labeled bone biopsy; and the finding of low trabecular bone volume. In such patients, preliminary data would suggest that oral bisphosphonates seem to be safe and effective down to GFR levels of 15 mL/min.

In patients with stage 5 CKD who are fracturing because of osteoporosis or who are on chronic glucocorticoids, reducing the oral bisphosphonate dosage to half of its usual prescribed dosing for PMO seems reasonable from known bisphosphonate pharmacokinetics, though we do need better scientific data to fully understand bisphosphonate usage in this population.
Treatment Maintenance hemodialysis
Maintenance peritoneal dialysis
Solid organ transplantation
Older patients undergoing dialysis treatment: cognitive functioning, depressive mood and health-related quality of life.

Tyrrell J, Paturel L, Cadec B, Capezzali E, Poussin G.

Laboratoire de Psychologie Clinique et de Psychopathologie, Universite Pierre Mendes France, Grenoble.

Aging Ment Health. 2005 Jul;9(4):374-9. Abstract quote  

An increasing number of older patients receive dialysis treatment to compensate for deficient kidneys due to end-stage renal disease (ESRD). Ethical questions arise about the benefits of dialysis when a patient appears unwilling or unable to comply with this treatment procedure. Such attitudes and behaviour may be due to psychological factors, but these are not routinely assessed.

The purpose of this study was to evaluate levels of cognitive impairment, depressive mood and self-reported quality of life in older dialysis patients (>70 years). A total of 51 outpatients receiving dialysis were assessed by psychologists, using a depression scale (MADRS), two cognitive tests (MMSE and BEC 96), and a quality of life questionnaire (NHP). Sixty percent of the patients were depressed, and between 30-47% had cognitive impairment. Almost half of the depressed patients were also cognitively impaired. The scores for self-reported quality of life varied widely within the sample. Cognitive impairment and depressive mood are often overlooked and underestimated in this population.

Regular assessments of depressive mood, cognitive ability and quality of life are recommended, given the prevalence of problems in these domains for older dialysis patients. The information obtained should assist staff as they reflect on individual cases where the benefits of continuing treatment are being examined.

Improving the Quality of Hemodialysis Treatment

A Community-Based Randomized Controlled Trial to Overcome Patient-Specific Barriers

Ashwini R. Sehgal, MD; Janeen B. Leon, MS, RD; Laura A. Siminoff, PhD; Mendel E. Singer, PhD; Lisa M. Bunosky, BA; Randall D. Cebul, MD

JAMA. 2002;287:1961-1967 Abstract quote

Mortality rates among US hemodialysis patients are the highest in the industrialized world at 23% per year. Measures of dialysis dose (Kt/V) correspond strongly with survival and are inadequate in one sixth of patients. Inadequate dialysis is also associated with increased hospitalizations and high inpatient costs. Our previous work identified 3 barriers to adequate hemodialysis: dialysis underprescription, catheter use, and shortened treatment time.

To determine the effect of a tailored intervention on adequacy of hemodialysis.

Design and Setting
Community-based randomized controlled trial with recruitment from April 1999 to June 2000 at 29 hemodialysis facilities in northeast Ohio.

Forty-four nephrologists and their 169 randomly selected adult patients receiving inadequate hemodialysis.

Nephrologists were randomly assigned to an intervention (n = 21) or control (n = 23) group. For patients in the intervention group (n = 85), depending on the barrier(s) present, a study coordinator gave nephrologists recommendations about optimizing dialysis prescriptions, expedited conversion of catheters to surgically created grafts or fistulas, and educated patients about the importance of compliance with treatment time. Patients in the control group (n = 84) continued to receive usual care.

Main Outcome Measures
Changes in Kt/V and specific barriers after 6 months.

At baseline, intervention and control patients had similar Kt/V measurements, specific barriers, and demographic and medical characteristics. After 6 months, intervention patients had 2-fold larger increases in Kt/V compared with control patients (+0.20 vs +0.10; P<.001) and were more likely to achieve their facility Kt/V goal (62% vs 42%; P = .01). Intervention patients also had nearly 3-fold larger increases in dialysis prescription (+0.16 vs +0.06; P<.001) and were 4 times more likely to change from use of catheters to use of fistulas/grafts (28% vs 7%; P = .04).

An intervention tailored to patient-specific barriers resulted in increased hemodialysis dose. Extending this approach to the 33 000 persons in the United States receiving inadequate hemodialysis may substantially enhance patient survival, diminish hospitalizations, and decrease inpatient expenditures.

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Last Updated February 14, 2006

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