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Abstract

Clinical Nephrology, Vol. 74 – No. 6/2010 (411-422)

Clinical and molecular characterization of a family with a dominant renin gene mutation and response to treatment with fludrocortisone

A.J. Bleyer¹*, M. Zivná²,³*, H. Hulková³, K. Hodanová²,³, P. Vyletal²,³, J. Sikora³, J. Zivný⁴, J. Sovová³, T.C. Hart⁵, J.N. Adams⁶, M. Elleder²,³, K. Kapp⁷, R. Haws⁸, L.D. Cornell⁹, S. Kmoch²,³ and P.S. Hart⁶

¹Section on Nephrology, Wake Forest University School of Medicine, Winston- Salem, NC, USA, ²Center for Applied Genomics, ³Institute for Inherited Metabolic Disorders, ⁴Institute of Pathophysiology, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic, ⁵Human Craniofacial Genetics Section, NIDCR, NIH, ⁶Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA, ⁷ZMBH (Center for Molecular Biology Heidelberg), University of Heidelberg, Heidelberg, Germany, ⁸Specialty Pediatrics, Marshfield, WI, and ⁹Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
Background: A family was identified with autosomal dominant inheritance of anemia, polyuria, hyperuricemia, and chronic kidney disease. Mutational analysis revealed a novel heterozygous mutation c.58T > C resulting in the amino acid substitution of cysteine for arginine in the preprorenin signal sequence (p.cys20Arg) occurring in all affected members. Methods: Effects of the identified mutation were characterized using in vitro and in vivo studies. Affected individuals were clinically characterized before and after administration of fludrocortisone. Results: The mutation affects endoplasmic reticulum co-translational translocation and posttranslational processing, resulting in massive accumulation of non-glycosylated preprorenin in the cytoplasm. This affects expression of intra-renal RAS components and leads to ultrastructural damage of the kidney. Affected individuals suffered from anemia, hyperuricemia, decreased urinary concentrating ability, and progressive chronic kidney disease. Treatment with fludrocortisone in an affected 10-year-old child resulted in an increase in blood pressure and estimated glomerular filtration rate. Conclusions: A novel REN gene mutation resulted in an alteration in the amino acid sequence of the renin signal sequence and caused childhood anemia, polyuria, and kidney disease. Treatment with fludrocortisone improved renal function in an affected child. Nephrologists should consider REN mutational analysis in families with autosomal dominant inheritance of chronic kidney disease, especially if they suffer from anemia, hyperuricemia, and polyuria in childhood.Correspondence to:
A.J. Bleyer, MD
Section on Nephrology
Wake Forest University
School of Medicine
Medical Center Blvd.
Winston-Salem, NC 27157, USA
Email: ableyer@wfubmc.edu

Abstract

Clinical Nephrology, Vol. 74 – No. 6/2010 (423-432)

The new kidney disease: improving global outcomes (KDIGO) guidelines – expert clinical focus on bone and vascular calcification

G. London¹, D. Coyne², K. Hruska³, H.H. Malluche⁴ and K.J. Martin⁵

¹Service de Néphrologie, Centre Hospitalier Manhès, Fleury Mérogis, France, ²Renal Division, Washington University School of Medicine, ³Department of Pediatrics, Renal Division, Washington University, Saint Louis, MO, ⁴Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Lexington, KY, and ⁵Division of Nephrology, Saint Louis University, Saint Louis, MO, USA
Chronic kidney disease-mineral and bone disorder (CKD-MBD) defines a triad of interrelated abnormalities of serum biochemistry, bone and the vasculature associated with chronic kidney disease (CKD). The new kidney disease: improving global outcomes (KDIGO) guidelines define the quality and depth of evidence supporting therapeutic intervention in CKD-MBD. They also highlight where patient management decisions lack a strong evidence base. Expert interpretation of the guidelines, along with informed opinion, where evidence is weak, may help develop effective clinical practice. The body of evidence linking poor bone health and reservoir function (the ability of bone to buffer calcium and phosphorus) with vascular calcification and cardiovascular outcomes is growing. Treating renal bone disease should be one of the primary aims of therapy for CKD. Evaluation of the biochemical parameters of CKD-MBD (primarily phosphorus, calcium, parathyroid hormone and vitamin D levels) as early as CKD Stage 3, and an assessment of bone status (by the best means available), should be used to guide treatment decisions. The adverse effects of high phosphorus intake relative to renal clearance (including stimulation of hyperparathyroidism) precede hyperphosphatemia, which presents late in CKD. Early reduction of phosphorus load may ameliorate these adverse effects. Evidence that calcium load may influence progression of vascular calcification with effects on mortality should also be considered when choosing the type and dose of phosphate binder to be used. The risks, benefits, and strength of evidence for various treatment options for the abnormalities of CKD-MBD are considered.Correspondence to:
Dr. G. London
Service de Néphrologie
Centre Hospitalier Manhès
8 rue Roger Clavier
91712 Fleury-Mérogis Cedex, France
Email: glondon@club-internet.fr

Abstract

Clinical Nephrology, Vol. 74 – No. 6/2010 (433-439)

Continuation of cinacalcet immediately after renal transplantation: a prospective cohort study

J. Aalten, J.F.M. Wetzels and A.J. Hoitsma

Department of Nephrology, Radboud University Nijmegen Medical Center, The Netherlands
Background: Cinacalcet is used for treating secondary hyperparathyroidism in dialysis patients, but it is currently unknown whether it can safely be continued immediately after renal transplantation. Methods: We prospectively studied renal transplant recipients with secondary hyperparathyroidism who were receiving cinacalcet before transplantation and continued treatment afterwards (n = 29) at a dose of 30 mg/day. Cinacalcet dose was titrated to serum calcium. Patients were followed for 6 months. Incidence of hypercalcemia, serum calcium and intact PTH (iPTH) were analyzed. Tacrolimus levels, acute rejection rate and renal function were compared with an age and sex matched control group. Results: In 16 patients hypercalcemia was observed after transplantation. Severe hypercalcemia (>= 2.87 mmol/l) (n = 4) and hypocalcemia (n = 2) were infrequent. No difference in acute rejection rate or renal function between the cinacalcet and the control group was found. There also was no clinically relevant influence of cinacalcet on tacrolimus levels. Conclusions: Our study shows that cinacalcet can safely be continued immediately after renal transplantation. Studies are needed to determine if continuation of cinacalcet is better than early withdrawal. Also, the optimum dose of cinacalcet and the long-term effects of cinacalcet after renal transplantation must be defined.Correspondence to:
J. Aalten, MD
Radboud University Nijmegen
Medical Center
Department of Nephrology, 464
P.O. Box 9101
6500 HB Nijmegen, The Netherlands
Email: j.aalten@nier.umcn.nl

Abstract

Clinical Nephrology, Vol. 74 – No. 6/2010 (440-445)

Experience with outpatient computed tomographic-guided renal biopsy

A. Margaryan, M.A. Perazella, R.L. Mahnensmith and A.K. Abu-Alfa

Section of Nephrology, Yale School of Medicine, New Haven, CT, USA
Native kidney biopsy is still performed primarily with hospital inpatient observation period. Experience with outpatient Computed Tomographic (CT)-guided renal biopsy at Yale New Haven Medical Center was studied to assess efficacy and safety. A total of 146 outpatient native kidney biopsies were identified between 1995 and 2001. Records were reviewed for demographics, clinical, and laboratory data and details of the procedure. Time of admission to the outpatient unit, duration of procedure and post-biopsy observation period were recorded. Complications such as bleeding, infection, admission to the hospital, transfusion, or intervention for continued bleeding were noted. Mean age was 43.9 ± 14.9 years and mean serum creatinine was 1.8 ± 1.4 mg/dl. Renal size averaged 11.4 cm. Post-procedure observation time of 4 – 6 h appeared to be adequate. Diagnostic tissue was successfully sampled in 98.6% of cases. Procedure was well tolerated with no hemodynamically significant changes. Hematocrit and hemoglobin concentration changes averaged 3.6 ± 2.5% and 1.0 ± 0.9 mg/dl, respectively (p < 0.001). There were no instances of death or need for intervention. Transfusion was required in 1 patient while 6 patients had detectable bleeding and were hospitalized for observation. Outpatient CT-guided kidney biopsy provides adequate tissue and appears to be safe with very low complication rates.Correspondence to:
A. Abu-Alfa, MD
P.O. Box 208029
333 Cedar Street
New Haven, CT 06520-8029, USA
Email: ali.abu-alfa@yale.edu

Abstract

Clinical Nephrology, Vol. 74 – No. 6/2010 (446-456)

Hepatitis C virus-related kidney disease: various histological patterns

K. Sumida, Y. Ubara, J. Hoshino, T. Suwabe, S. Nakanishi, R. Hiramatsu, E. Hasegawa, N. Hayami, M. Yamanouchi, N. Sawa, F. Takemoto, K. Takaichi and K. Oohashi

Nephrology Center and Department of Pathology, Toranomon Hospital Kajigaya, Kanagawa, Japan
Background: Although hepatitis C virus (HCV) infection is known to be associated with Type 2 cryoglobulinemic glomerulopathy (CG), only a few reports about other types of nephropathy have been published. Methods: 68 HCV antibody positive patients in whom renal biopsy had been performed for persistent proteinuria, hematuria, and/or renal dysfunction between 1992 and 2008 at our institute were included. The histological, clinical and laboratory characteristics including the age, gender, hypertension, diabetes mellitus, liver histology (chronic hepatitis or liver cirrhosis), HCV-RNA, HCV genotype, splenomegaly, gastroesophageal varices, serum creatinine, hemoglobin, platelet count, rheumatoid factor, cryoglobulin, IgG, IgA, IgM, CH50, C3, C4, creatinine clearance, 24-h protein excretion, and hematuria, between their nephropathy with and without immune deposition were compared. Results: Nephropathy was classified into two groups based on the detection of immune deposits by immunofluorescence microscopy: i.e., a positive group (n = 39) and a negative group (n = 29). The former group was further classified into three types of nephropathy: IgG dominant group (n = 10) (including membranous nephropathy (MN)), IgA dominant group (n = 20) (including IgA nephropathy (IgAN)), membranoproliferative glomerulonephritis (MPGN) (IgA type)), and IgM dominant group (n = 9) (MPGN apart from the IgA type). The latter group included diabetic nephropathy (n = 13), focal glomerular sclerosis (n = 4), and benign nephrosclerosis (n = 3), malignant nephrosclerosis (n = 1), tubulointerstitial nephritis (TIN) (n = 2), minimal change nephrotic syndrome (n = 1), cast nephropathy (n = 1), granulomatous TIN (n = 1), and others (n = 3). An increased serum IgM level, hypocomplementemia, splenomegaly, thrombocytopenia, liver cirrhosis, hematuria, and a high HCV RNA level were features of patients with MPGN of IgM dominant group (consistent with “CG”). Conclusions: Our results showed various histological patterns of HCV-related kidney disease and the specificity of CG, and revealed that a minority of HCV patients (n = 7) presented typical CG, while IgAN, MN, and diabetic nephropathy were more frequent.Correspondence to:
K. Sumida, MD
Nephrology Center
Toranomon Hospital Kajigaya
1-3-1, Kajigaya, Takatsu-ku
Kawasaki, Kanagawa, 213-0015, Japan
Email: k_sumida0504@yahoo.co.jp

Abstract

Clinical Nephrology, Vol. 74 – No. 6/2010 (457-464)

Exocrine pancreatic function in patients with end-stage renal disease

J. Griesche-Philippi¹, J. Otto², H. Schwörer², P. Maisonneuve³ and P.G. Lankisch⁴

¹Practice for Nephrology and Dialysis, Lüneburg, ²Division of Gastroenterology and Endocrinology, Department of Internal Medicine, University of Göttingen, Göttingen, Germany, ³European Institute of Oncology, Milan, Italy, and ⁴Clinic for General Internal Medicine, Medical Center, Municipal Clinic of Lüneburg, Lüneburg, Germany
Aim: Malnutrition is a common problem in patients with end-stage renal disease (ESRD). Several studies showed 30 years ago that more than half of patients with ESRD suffered from exocrine pancreatic insufficiency. However, the studies never investigated whether the functional impairments led to morphological changes of the pancreas or to steatorrhea and thus indicating the need for lifelong pancreatic enzyme substitution. Our goal was therefore not only to establish the frequency but also the severity of exocrine pancreatic insufficiency in hemodialysis patients. Methods: The study included 50 hemodialysis patients with no history of acute or chronic pancreatitis or upper abdominal symptoms of uncertain origin. All patients with hyperthyroidism, status post-gastrectomy or (partial) small bowel resection, or chronic inflammatory bowel disease were excluded. In all 50 patients, fecal elastase-1 was determined using two different methods (Bioserv Diagnostics and ScheBo Biotech) and fecal fat content and fecal weight were measured. Results: Mild to moderate exocrine pancreatic insufficiency (elastase-1 100 – 200 µg/g stool) was found in 10% of patients. It was not correlated with age, sex, and underlying renal disease, duration of hemodialysis, or diarrhea and steatorrhea. In no patient was the enzyme content < 100 µg/g stool, i.e., it never sank to a level at which pancreatic enzyme substitution would have been recommended. Nine patients (18%) had mild diarrhea (200 – 300 g stool/ day), and 10 (20%) had mild steatorrhea (7 – 15 g fat/day in the stool). Five patients had both diarrhea and steatorrhea. Conclusions: Mild to moderate but not severe exocrine pancreatic insufficiency is not infrequent in patients on hemodialysis but unlikely to be responsible for malnutrition in ESRD. Non-pancreas-related steatorrhea is also not uncommon. This finding requires further analysis because steatorrhea might influence nutrition, thus potentially opening the way to new therapeutic approaches.Correspondence to:
Prof. Dr. P.G. Lankisch
Reiherstieg 23
21337 Lüneburg, Germany
Email: Paulgeorg.lankisch@t-online.de

Abstract

Clinical Nephrology, Vol. 74 – No. 6/2010 (465-470)

Enhanced degradation of tryptophan in patients on hemodialysis

P. Koenig¹, C. Nagl², G. Neurauter², H. Schennach⁴, G. Brandacher³ and D. Fuchs²

¹Department of Internal Medicine, ²Division of Biological Chemistry, Biocenter, ³Department of Surgery, Innsbruck Medical University, and ⁴Central Institute of Blood Transfusion and Immunology, University Clinics, Innsbruck, Austria
Background: Hemodialysis patients often present with increased concentrations of tryptophan catabolites perhaps related to an enhanced activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) that is inducible by pro-inflammatory stimuli. The often chronic inflammation and immune activation status in dialysis patients may accelerate tryptophan degradation, which could influence patients’ psychological performance. Patients and methods: In this study, plasma concentrations of kynurenine and tryptophan were determined by HPLC in 75 dialysis patients, aged 65.3 ± 15.0 years. Forty patients were female, 35 male; 21 (28%) had diabetes mellitus Type 1 or 2 and 32 (43%) suffered from sleep disturbances and/or depression. Their dialysis vintage was 4.26 ± 4.72 years. HPLC results were compared to concentrations obtained from 40 healthy blood donors, to immune activation marker neopterin, and to psychological test results based on INTERMED scores. Results: Compared to those in healthy controls, tryptophan concentrations were decreased in patients. Neopterin, kynurenine and the kynurenine to tryptophan ratio (kyn/trp, an index of tryptophan degradation) were increased in patients (all p < 0.01). Kyn/trp correlated with neopterin concentrations (rs = 0.393, p < 0.01). INTERMED scores were 21.0 + 8.4 and slightly higher in females (U = –1.831, p < 0.07); they correlated with tryptophan concentrations (rs = –0.227, p < 0.05) but with no other parameter studied. Data point to a possible relationship between tryptophan metabolic disturbances and psychologic presentation of patients, although only a rather weak relationship was found. Conclusion: We conclude that tryptophan degradation is increased in dialysis patients. The association with increased neopterin concentrations indicates activated IDO.Correspondence to:
Dr. D. Fuchs
Division of Biological Chemistry Biocenter, Innsbruck Medical University
Fritz Pregl Straße 3, 6020 Innsbruck, Austria
Email: dietmar.fuchs@i-med.ac.at

Abstract

Clinical Nephrology, Vol. 74 – No. 6/2010 (471-473)

Atypical electrolyte kinetics during an emergency dialysis session in a patient with Leriche syndrome

S. Koball¹, H. Hickstein¹, A. Führer¹, T. Heller², J. Stange¹ and S. Mitzner¹

¹Department of Internal Medicine and Nephrology and ²Department of Radiology, University of Rostock, Rostock, Germany
A hemodialysis patient suffered from circulation failure due to a low output syndrome caused by a hyperkalemia (9.9 µmol/l) with typical ecg signs. An emergency hemodialysis was started. After 2 h ecg signs of hypokalemia (2.1 µmol/l) were detectable. Hemodialysis was stopped. 2 h later, serum potassium rose to 6.2 µmol/l. An obturation of the aorta and the inferior caval vein with perfusion through collateral vessels of the lower body side was obvious, resulting into a faster electrolyte correction in the upper and a delayed correction in the lower body side with a rebound in the upper compartment. Dialysis time and dialysate potassium (4.0 µmol/l) were increased. Furthermore no potassium problems occurred.Correspondence to:
Dr. med. S. Koball
University of Rostock
Department of Internal Medicine/Nephrology
Ernst-Heydemann-Straße 6
18055 Rostock, Germany
Email: Sebastian.koball@medizin.uni-rostock.de

Abstract

Clinical Nephrology, Vol. 74 – No. 6/2009 (474-479)

Acute postinfectious glomerulonephritis associated with Campylobacter jejuni enteritis – a case report and review of the literature on C. jejuni’s potential to trigger immunologically mediated renal disease

M. op den Winkel¹, V. Gülberg¹, M. Weiss², F. Ebeling³, A.L. Gerbes¹ and W. Samtleben⁴

¹Department of Medicine II, ²Institute of Pathology, ³Kuratorium Kidney Center Munich-Neuried, ⁴Division of Nephrology, Department of Medicine I, University-Hospital Munich-Großhadern, Ludwig-Maximilians-University, Munich, Germany
Kidney disease is a rare complication of Campylobacter jejuni (C. jejuni) enteritis. We here present the case of an 18-year-old male patient with crampy abdominal pain, vomiting, diarrhea, and fever. Three weeks later urinalysis revealed mild proteinuria and hematuria and a marked raise in serum creatinine was observed. Renal biopsy demonstrated acute endocapillary glomerulonephritis with mesangial IgM (immunoglobuline M) deposits. Extensive workup revealed no signs of skin or joint disease, thus excluding Henoch-Schönlein purpura. Due to persistent abdominal discomfort further gastro-enterological tests were performed and eventually Campylobacter jejuni was isolated from the patient’s feces. In the absence of other precipitating factors for renal diseases we presumed an association between the bacterial infection and this postinfectious glomerulonephritis. Over a time period of 6 months the patient’s kidney function normalized completely. However, long-term prognosis remains unclear. In addition to the case report, we conducted a review of the literature with results underlining Campylobacter jejuni’s potential to trigger various types of immune mediated kidney diseases.Correspondence to:
Dr. M. op den Winkel
Department of Medicine II
University-Hospital Munich-Großhadern
Marchioninistraße 15, 81377 Munich, Germany
Email: Mark.op.den.Winkel@med.uni-muenchen.de

Abstract

Clinical Nephrology, Vol. 74 – No. 6/2010 (480-484)

Malignant lymphoma of the kidney mimicking rapid progressive glomerulonephritis

S.-C. Weng¹, K.-H. Shu¹,⁴, M.-C. Wen², C.-H. Cheng¹,⁴, M.-J. Wu¹, T.-M. Yu¹, Y.-W. Chuang¹ and C.-H. Chen¹,³,⁵

¹Division of Nephrology, Department of Internal Medicine, ²Department of Pathology, Taichung Veterans General Hospital, Taichung, ³School of Medicine, College of Medicine, China Medical University, Taichung, ⁴School of Medicine, Chung-Shan Medical University, Taichung, and ⁵Department of Life Science, Tunghai University, Taichung, Taiwan
Primary renal lymphoma (PRL) is rare and often presents as rapidly progressive renal failure. Most cases of PRL are large-cell lymphomas of B-cell lineage. Herein, we report a 75-year-old female patient with infiltrative CD20 (+) B-cell lymphoma who underwent 4 consecutive courses of chemotherapy with R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone) and after 12 sessions became free from hemodialysis in good general condition. Her serum creatinine level gradually decreased to 4.1 mg/dl with adequate urine output. Unfortunately, a relapse of CD20 (–) lymphoma developed rapidly involving other organs. She died with severe hospital-acquired pneumonia and febrile neutropenia after the last chemotherapy with R-MINE almost 1 year after onset of symptoms. We conclude that renal biopsy enables prompt diagnosis in rapidly progressive renal failure and immunophenotyping and also staging workup of the lymphoma in case of positive biopsy. Though rituximab improved response rate of PRL, it reduced expression of CD20. This may relate to frequent relapse/resistance after rituximab therapy and poor long-term patient survival.Correspondence to:
C.-H. Chen, MD
Division of Nephrology
Department of Internal Medicine
Taichung Veterans General Hospital 160, Section 3
Taichung-Kang Rd, Taichung, 407 Taiwan
Email: cschen920@yahoo.com

Abstract

Clinical Nephrology, Vol. 74 – No. 6/2010 (485-490)

Chronic periaortitis associated with membranous nephropathy: clues to common pathogenetic mechanisms

A. Palmisano¹, D. Corradi², M.L. Carnevali¹, F. Alberici¹, E.M. Silini², R. Gatti³, L. Allegri¹, C. Buzio¹ and A. Vaglio¹

¹Department of Clinical Medicine, Nephrology and Health Science, ²Department of Pathology and Laboratory Medicine, Section of Pathology, and ³Department of Experimental Medicine, Section of Histology, University of Parma, Italy
Chronic periaortitis (CP) is a rare disease hallmarked by the presence of a periaortic retroperitoneal fibro-inflammatory tissue which can often cause obstructive uropathy. CP is isolated in most cases but it may also be associated with other sclerosing inflammatory and immune-mediated diseases. We here present the case of a patient who was initially diagnosed as having CP and subsequently developed membranous nephropathy and chronic sclerosing sialoadenitis of the right parotid gland. As these conditions were all characterized by either pronounced infiltration of IgG4-positive plasma cells or marked IgG4 tissue deposition, we hypothesize that they are part of the same disease spectrum, and discuss the immune-mediated pathogenetic mechanisms potentially shared by these conditions. In particular, we consider the role of Th2-mediated immune reactions and of immunogenetic factors such as HLA genotype as common determinants of these disorders.Correspondence to:
Dr. A. Vaglio
Department of Clinical Medicine, Nephrology and Health Science
University of Parma
Via Gramsci 14
43100 Parma, Italy
Email: augusto.vaglio@virgilio.it

Abstract

Peritonitis after gynecological and gastroscopic examinations in a peritoneal dialysis patient

S. Morimoto, E. Kido, M. Higashi, N. Sumitani, H. Takagishi, S. Kakimoto, K. Someya, T. Morita, T. Iwasaka, K. Suzuki and A. Yasui

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Volume 74, No. 6/2010(December)