DOCSLIB.ORG

Crystalline Light Chain Proximal Tubulopathy and Podocyto- Pathy: a Case Report Tubulopatia Proximal E Podocitopatia De Cadeias Leves Cristalinas: Relato De Caso

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Crystalline Light Chain Proximal Tubulopathy and Podocyto- Pathy: a Case Report Tubulopatia Proximal E Podocitopatia De Cadeias Leves Cristalinas: Relato De Caso CLINICOPATHOLOGICAL CASE | CASO CLÍNICO-PATOLÓGICO Crystalline light chain proximal tubulopathy and podocyto- pathy: a case report Tubulopatia proximal e podocitopatia de cadeias leves cristalinas: relato de caso Authors CASE PRESENTATION A renal ultrasound showed a right kidney Ankit B. Patel1 of 11.9 cm with mild fullness of collect- 1 In this case report we present a 64-year- John Y. Choi ing system and a left kidney of 10.4 cm 2 old man with a history of IgG kappa para- Walter P. Mutter with no signs of hydronephrosis. A bone Astrid Weins3 proteinemia for 14 years with no signs of marrow biopsy 1.5 years prior to presen- Leonardo V. Riella1 multiple myeloma or plasmacytoma who tation showed findings consistent with presented to the renal clinic with new on- a plasma cell dyscrasia but did not meet set hypokalemia and increase in serum 1 Harvard Medical School, Renal criteria for myeloma. Plasma cells were creatinine. His past medical history was Division, Brigham & Women’s 5% without lymphoid infiltrates. Flow Hospital, Boston, MA, EUA. remarkable for a diagnosis of necrobiotic 2 cytometry showed abnormal plasma cells Harvard Medical School, Renal xanthogranuloma for 30 years treated with Division, Newton Wellesley that were kappa restricted. Cytogenetics multiple modalities including chlorambucil, Hospital, Boston, MA, EUA. were normal. 3 Harvard Medical School, thalidomide, cryotherapy, intravenous im- Brigham & Women’s Hospital, munoglobulin, and electron beam therapy. Department of Pathology, Boston, DIFFERENTIAL DIAGNOSIS MA, EUA. He also had a history of squamous cell car- cinoma, melanoma, bilateral carotid artery A middle age patient presented with new- disease, coronary artery disease, and hyper- onset renal dysfunction, worsening albu- tension. He had no fevers, cough, dyspnea, minuria, and increased urinary frequency abdominal pain, nausea, or vomiting but and thirst. His evaluation was notable for did complain of a worsening headache over a urinalysis with no blood but urine total the last week. He also reported increased protein/creatinine of 2.94 g/g and urine urinary frequency and thirst but denied albumin/creatinine of 1.68 g/g. The new any dysuria or hematuria. His medications onset of proteinuria along with renal dys- included aspirin, clopidogrel, amlodipine, function helped guide the differential diag- carvedilol, hydralazine, and atorvastatin. nosis for acute kidney injury. Proteinuria He started no new medications and report- generally is categorized as tubular or ed no sick contacts. His blood pressure was glomerular in origin. Given the history 152/82 mmHg. On physical examination, of paraproteinemia, the new increase in the patient appeared comfortable with a proteinuria could result from an increase clear oropharynx, cardiac exam with regu- in the paraprotein burden. Given the lar rate and rhythm and no murmurs, rubs, modest level of free light chains and that or gallops, clear lung sounds, soft and non- more than half of the total protein found tender abdomen, no lower extremity ede- in the urine was albumin, the proteinuria ma, and numerous erythematous plaques was not due to increased urinary free light chains but rather glomerular in origin. Submitted on: 04/30/2019. on his trunk and extremities. His initial labs Approved on: 08/23/2019. at presentation are summarized in Table 1. The paraprotein can cause glomerular in- Of note, his creatinine was 1.0 mg/dL 10 jury leading to albuminuria. Proteinuria can also be associated with proximal tu- Correspondence to: months prior. Urine sediment examina- Leonardo V. Riella. tion showed occasional epithelial cells and bule dysfunction, which is considered low E-mail: lriella@bwh.harvard.edu white blood cells as well as hyaline casts. molecular weight proteinuria and there is DOI: 10.1590/2175-8239-JBN-2019-0086 99 A chain of crystals TABLE 1 INITIAL LABORATORY VALUES Variable Reference Range Lab value Blood Sodium (mmol/L) 137-146 139 Potassium (mmol/L) 3.5-5.3 3.2 Chloride (mmol/L) 98-107 96 Carbon dioxide (mmol/L) 23-32 27 Urea nitrogen (mg/dL) 5-25 21 Creatinine (mg/dL) 0.6-1.4 1.69 Glucose (mg/dL) 70-100 120 Calcium (mg/dL) 8.6-10.3 8.9 Albumin (g/dL) 4.0-5.0 3.1 Phosphorous (mg/dL) 2.7-4.5 3.2 Magnesium (mg/dL) 1.3-2.7 1. 7 Uric Acid (mg/dL) 2.6-6.0 5.6 Aspartate aminotransferase (U/L) 6-40 30 Alanine aminotransferase (U/L) 10-49 18 Alkaline phosphatase (U/L) 35-130 76 Total Bilirubin (mg/dL) 0-1.0 0.4 Hemoglobin (g/dL) 12.0-17.0 11. 6 Hematocrit (%) 35.0-50.0 35.2 White-cell count (per mm3) 4,500-11,000 8,900 Platelet count (per mm3) 150,000-400,000 265,000 Kappa light chains (mg/dL) 3.3-19.4 48.7 Lambda light chains (mg/dL) 5.7-26.3 1.53 Free Kappa/lambda ratio 0.26-1.65 31.9 M-spike, SPEP (g/dL) None 1.19 IgG Kappa Urine Urinalysis Blood Negative Negative Glucose Negative Negative Protein Negative ++ Specific gravity 1.000-1.035 1. 011 pH 5.0-8.0 7. 0 Sediment Red blood cell (/hpf) 0-3 2 White blood cell (/hpf) 0-4 1 Casts Negative Negative Crystals Negative Negative Chemistry Spot urine protein/creatinine (g/g) < 0.15 2.94 Spot urine microalbumin/creatinine (g/g) 0-0.03 1.68 Urine potassium/Cr (mEq/g) 0-14 49.7 Urine M spike (mg/24hr) None 244 IgG Kappa Urine total protein (g/24hrs) < 0.08 2.2 Braz. J. Nephrol. (J. Bras. Nefrol.) 2020;42(1):99-105 100 A chain of crystals a larger difference between urinary total protein and monoclonal gammopathy (MG) was categorized into albumin excretion. Although tubular injury can lead monoclonal gammopathy of unknown significance to albuminuria, it is not typically to the degree not- (MGUS), smoldering multiple myeloma (SMM), and ed in this case. The patient had a significant cancer multiple myeloma (MM) based on: 1) monoclonal history, although no new treatment during the time protein quantification on protein electrophoresis, 2) course of the renal dysfunction and no signs of recur- monoclonal plasma cell percentage on bone marrow rence of skin cancer. Of note, he did have new onset biopsy, and 3) evidence of end organ damage such as hypokalemia with urine chemistry suggestive of po- renal failure. While this system offered some useful tassium wasting and a known underlying IgG kappa insight on risk stratification and prognosis, a signifi- paraproteinemia. cant proportion of MGUS population developed pro- gressive renal disease. This observation added a new HYPOKALEMIA category to the previous classification: monoclonal Hypokalemia is uncommonly associated with acute gammopathy of renal significance (MGRS)1. A study kidney injury. To determine the etiology of hypoka- conducted between January 2000 and August 2016 lemia, it is important to first identify if there is a de- found 44 of 2,935 MGUS patients during that time crease in potassium intake, an increase in potassium were diagnosed with MGRS suggesting up to 1.5% of output, or a transcellular shift of potassium. The el- MGUS patients have renal complications attributed evated spot urinary potassium/creatinine ratio in this to their monoclonal gammopathy2. MGRS is further patient prior to potassium supplementation suggested categorized based on the presence and type of orga- increase urinary potassium excretion as the etiology nized deposits (Figure 1). If organized deposits are of hypokalemia. Urinary potassium wasting can result detected, the histopathology can be diagnosed based from a number of different causes including: 1) genet- on the shapes and sizes on the deposits. Fibrillary de- ic defects in tubular sodium reabsorption increasing posits are usually 7-12 nm; immunotactoids are 17- distal sodium delivery, a key regulator of potassium 52 nm hollow centered microtubules; and crystalline excretion, 2) hypomagnesemia, which decreases tonic can present with various sizes and shapes usually in inhibition of secretory potassium channels, 3) varied rhomboid or needle form. forms of hyperaldosteronism leading to upregulation of sodium and potassium conductances in the con- HISTOPATHOLOGY necting tubule and collecting duct, or 4) increase in LIGHT MICROSCOPY (LM) urinary anions (e.g. bicarbonate) that are excreted A kidney biopsy was completed for further evalu- with countercations such as potassium to maintain ation. Figure 2a shows Periodic Acid Schiff (PAS) electroneutrality. Hypokalemia with acute kidney stained kidney section with three glomeruli with injury is a unique feature of leptospirosis, however, varied degrees of chronic changes: one glomerulus there was no recent travel or other clinical signs to is globally sclerosed, another glomerulus shows fea- suggest infection. Given the history of paraprotein- tures of collapsing glomerulopathy, and the third emia and high urinary pH, proximal tubule dysfunc- glomerulus has mild mesangial expansion. There are tion with proximal renal tubular acidosis (pRTA) some interspersed normal appearing tubules, some was suspected since it may lead to bicarbonate uri- hypertrophic with obvious PAS-positive protein reab- nary wasting and associated hypokalemia. Proximal sorption granules in the cytoplasm along with basal tubulopathy from paraproteinemia is often associat- nuclei (yellow arrow), while adjacent tubules reveal ed with global proximal tubule dysfunction (Fanconi PAS-negative lacy cytoplasm (blue arrow) (Figure 2c). syndrome). However, this patient had normal serum Figure 2b shows a higher magnification of a glomeru- levels of phosphorus and uric acid with no evidence lus with collapsing features, including extensive pro- of glucosuria indicating that some functions of the tein reabsorption granules in multiple epithelial cells proximal tubule remain preserved. and a collapsed tuft. MONOCLONAL GAMMOPATHY WITH RENAL DISEASE IMMUNOFLUORESCENCE (IF) Monoclonal paraproteins can have an array of dif- Figure 3a and b shows an IF stain on paraffin sections ferent effects on the kidney.
Load more

Recommended publications
  • Inherited Renal Tubulopathies—Challenges and Controversies
    G C A T T A C G G C A T genes Review Inherited Renal Tubulopathies—Challenges and Controversies Daniela Iancu 1,* and Emma Ashton 2 1 UCL-Centre for Nephrology, Royal Free Campus, University College London, Rowland Hill Street, London NW3 2PF, UK 2 Rare & Inherited Disease Laboratory, London North Genomic Laboratory Hub, Great Ormond Street Hospital for Children National Health Service Foundation Trust, Levels 4-6 Barclay House 37, Queen Square, London WC1N 3BH, UK; emma.ashton@gosh.nhs.uk * Correspondence: d.iancu@ucl.ac.uk; Tel.: +44-2381204172; Fax: +44-020-74726476 Received: 11 February 2020; Accepted: 29 February 2020; Published: 5 March 2020 Abstract: Electrolyte homeostasis is maintained by the kidney through a complex transport function mostly performed by specialized proteins distributed along the renal tubules. Pathogenic variants in the genes encoding these proteins impair this function and have consequences on the whole organism. Establishing a genetic diagnosis in patients with renal tubular dysfunction is a challenging task given the genetic and phenotypic heterogeneity, functional characteristics of the genes involved and the number of yet unknown causes. Part of these difficulties can be overcome by gathering large patient cohorts and applying high-throughput sequencing techniques combined with experimental work to prove functional impact. This approach has led to the identification of a number of genes but also generated controversies about proper interpretation of variants. In this article, we will highlight these challenges and controversies. Keywords: inherited tubulopathies; next generation sequencing; genetic heterogeneity; variant classification. 1. Introduction Mutations in genes that encode transporter proteins in the renal tubule alter kidney capacity to maintain homeostasis and cause diseases recognized under the generic name of inherited tubulopathies.
    [Show full text]
  • Effects of Ramipril in Nondiabetic Nephropathy: Improved Parameters of Oxidatives Stress and Potential Modulation of Advanced Glycation End Products
    Journal of Human Hypertension (2003) 17, 265–270 & 2003 Nature Publishing Group All rights reserved 0950-9240/03 $25.00 www.nature.com/jhh ORIGINAL ARITICLE Effects of ramipril in nondiabetic nephropathy: improved parameters of oxidatives stress and potential modulation of advanced glycation end products KSˇ ebekova´1, K Gazdı´kova´1, D Syrova´2, P Blazˇı´cˇek2, R Schinzel3, A Heidland3, V Spustova´1 and R Dzu´ rik 1Institute of Preventive and Clinical Medicine, Bratislava, Slovakia; 2Military Hospital, Bratislava, Slovakia; 3University Wuerzburg, Germany Enhanced oxidative stress is involved in the progres- patients on conventional therapy did not differ signifi- sion of renal disease. Since angiotensin converting cantly from the ramipril group, except for higher Hcy enzyme inhibitors (ACEI) have been shown to improve levels in the latter. Administration of ramipril resulted in the antioxidative defence, we investigated, in patients a drop in blood pressure and proteinuria, while creati- with nondiabetic nephropathy, the short-term effect of nine clearance remained the same. The fluorescent the ACEI ramipril on parameters of oxidative stress, AGEs exhibited a mild but significant decline, yet CML such as advanced glycation end products (AGEs), concentration was unchanged. The AOPP and malon- advanced oxidation protein products (AOPPs), homo- dialdehyde concentrations decreased, while a small rise cysteine (Hcy), and lipid peroxidation products. Ramipril in neopterin levels was evident after treatment. The (2.5–5.0 mg/day) was administered to 12 newly diag- mentioned parameters were not affected significantly in nosed patients for 2 months and data compared with a the conventionally treated patients. Evidence that rami- patient group under conventional therapy (diuretic/ pril administration results in a mild decline of fluores- b-blockers) and with age- and sex-matched healthy cent AGEs is herein presented for the first time.
    [Show full text]
  • April 2020 Radar Diagnoses and Cohorts the Following Table Shows
    RaDaR Diagnoses and Cohorts The following table shows which cohort to enter each patient into on RaDaR Diagnosis RaDaR Cohort Adenine Phosphoribosyltransferase Deficiency (APRT-D) APRT Deficiency AH amyloidosis MGRS AHL amyloidosis MGRS AL amyloidosis MGRS Alport Syndrome Carrier - Female heterozygote for X-linked Alport Alport Syndrome (COL4A5) Alport Syndrome Carrier - Heterozygote for autosomal Alport Alport Syndrome (COL4A3, COL4A4) Alport Syndrome Alport Anti-Glomerular Basement Membrane Disease (Goodpastures) Vasculitis Atypical Haemolytic Uraemic Syndrome (aHUS) aHUS Autoimmune distal renal tubular acidosis Tubulopathy Autosomal recessive distal renal tubular acidosis Tubulopathy Autosomal recessive proximal renal tubular acidosis Tubulopathy Autosomal Dominant Polycystic Kidney Disease (ARPKD) ADPKD Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) ADTKD Autosomal Recessive Polycystic Kidney Disease (ARPKD) ARPKD/NPHP Bartters Syndrome Tubulopathy BK Nephropathy BK Nephropathy C3 Glomerulopathy MPGN C3 glomerulonephritis with monoclonal gammopathy MGRS Calciphylaxis Calciphylaxis Crystalglobulinaemia MGRS Crystal-storing histiocytosis MGRS Cystinosis Cystinosis Cystinuria Cystinuria Dense Deposit Disease (DDD) MPGN Dent Disease Dent & Lowe Denys-Drash Syndrome INS Dominant hypophosphatemia with nephrolithiasis or osteoporosis Tubulopathy Drug induced Fanconi syndrome Tubulopathy Drug induced hypomagnesemia Tubulopathy Drug induced Nephrogenic Diabetes Insipidus Tubulopathy Epilepsy, Ataxia, Sensorineural deafness, Tubulopathy
    [Show full text]
  • Prime Mover and Key Therapeutic Target in Diabetic Kidney Disease
    Diabetes Volume 66, April 2017 791 Richard E. Gilbert Proximal Tubulopathy: Prime Mover and Key Therapeutic Target in Diabetic Kidney Disease Diabetes 2017;66:791–800 | DOI: 10.2337/db16-0796 The current view of diabetic kidney disease, based on estimated glomerular filtration rate (eGFR) decline (2). In meticulously acquired ultrastructural morphometry and recognition of these findings, the term diabetic kidney the utility of measuring plasma creatinine and urinary al- disease rather than diabetic nephropathy is now commonly bumin, has been almost entirely focused on the glomer- used. On the background of recent advances in the role of ulus. While clearly of great importance, changes in the the proximal tubule as a prime mover in diabetic kidney PERSPECTIVES IN DIABETES glomerulus are not the major determinant of renal prog- pathology, this review highlights key recent developments. nosis in diabetes and may not be the primary event in the Published mostly in the general scientific and kidney- development of diabetic kidney disease either. Indeed, specific literature, these advances highlight the pivotal advances in biomarker discovery and a greater appreci- role this part of the nephron plays in the initiation, pro- ation of tubulointerstitial histopathology and the role of gression, staging, and therapeutic intervention in diabetic tubular hypoxia in the pathogenesis of chronic kidney kidney disease. From a pathogenetic perspective, as illus- disease have given us pause to reconsider the current trated in Fig. 1 and as elaborated on further in this review, “glomerulocentric” paradigm and focus attention on the proximal tubule that by virtue of the high energy require- tubular hypoxia as a consequence of increased energy de- ments and reliance on aerobic metabolism render it par- mands and reduced perfusion combine with nonhypoxia- ticularly susceptible to the derangements of the diabetic related forces to drive the development of tubular atrophy fi state.
    [Show full text]
  • 1 Fludrocortisone- a Treatment for Tubulopathy Post Paediatric Renal Transplantation: a National Paediatric Nephrology Unit Experience
    Fludrocortisone- a treatment for tubulopathy post paediatric renal transplantation: A national paediatric nephrology unit experience Ali SR1, Shaheen I1, Young D2, Ramage I1, Maxwell H1, Hughes DA1, Athavale D1, Shaikh MG3 1. Department of Paediatric Nephrology, Royal Hospital for Children, 1345 Govan Road, Glasgow, UK, G51 4TF. 2. Department of Mathematics and Statistics, University of Strathclyde, 16 Richmond Street, Glasgow, UK, G1 1XQ. 3. Department of Paediatric Endocrinology and Diabetes, Royal Hospital for Children, 1345 Govan Road, Glasgow, UK, G51 4TF. Correspondence Dr MG Shaikh Department of Paediatric Endocrinology and Diabetes, Royal Hospital for Children, 1345 Govan Road, Glasgow, UK. G51 4TF Email: guftar.shaikh@nhs.net Tel: 0141 451 6548 1 Fludrocortisone- a treatment for tubulopathy post paediatric renal transplantation: A national paediatric nephrology unit experience Ali SR, Shaheen I, Young D, Ramage I, Maxwell H, Hughes DA, Athavale D, Shaikh MG Pediatr Transplantation 2017 ABSTRACT Background Calcineurin inhibitors post renal transplantation are recognised to cause tubulopathies in the form of hyponatremia, hyperkalemia and acidosis. Sodium supplementation may be required, increasing medication burden and potentially resulting in poor compliance. Fludrocortisone has been beneficial in addressing tubulopathies in adult studies, with limited paediatric data available. Methods A retrospective review of data from an electronic renal database from December 2014 to January 2016. Results 47 post-transplant patients were reviewed with 23 (49%) patients on sodium chloride or bicarbonate. 9 patients, aged 8.3 years (range 4.9- 16.4) commenced fludrocortisone 22 months (range 1-80) after transplant and were followed up for 9 months (range 2-20). All patients stopped sodium bicarbonate; all had a reduction or no increase in total daily doses of sodium chloride.
    [Show full text]
  • Advanced Oxidation Protein Products Contribute to Renal Tubulopathy Via Perturbation Of
    Kidney360 Publish Ahead of Print, published on June 3, 2020 as doi:10.34067/KID.0000772019 Advanced oxidation protein products contribute to renal tubulopathy via perturbation of renal fatty acids Tadashi Imafuku1,2, Hiroshi Watanabe1,§, Takao Satoh3, Takashi Matsuzaka4,5, Tomoaki Inazumi6, Hiromasa Kato1, Shoma Tanaka1, Yuka Nakamura1, Takehiro Nakano1, Kai Tokumaru1, Hitoshi Maeda1, Ayumi Mukunoki7, Toru Takeo7, Naomi Nakagata7, Motoko Tanaka8, Kazutaka Matsushita8, Soken Tsuchiya6, Yukihiko Sugimoto6, Hitoshi Shimano4,9, Masafumi Fukagawa10, Toru Maruyama1,§ 1Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan 2Program for Leading Graduate Schools "HIGO (Health life science: Interdisciplinary and Glocal Oriented) Program", Kumamoto University, Kumamoto, Japan 3Kumamoto Industrial Research Institute, Kumamoto, Japan 4Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, University of Tsukuba, Ibaraki, Japan 5Transborder Medical Research Center, University of Tsukuba, Ibaraki, Japan 6Department of Pharmaceutical Biochemistry, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan 7Division of Reproductive Engineering, Center for Animal Resources and Development (CARD), Kumamoto University, Kumamoto, Japan 8Department of Nephrology, Akebono Clinic, Kumamoto, Japan. 1 Copyright 2020 by American Society of Nephrology. 9AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo, Japan 10Division of Nephrology,
    [Show full text]
  • Reversible Proximal Renal Tubular Dysfunction After One-Time Ifosfamide Exposure
    Cancer Res Treat. 2010;42(4):244-246 DOI 10.4143/crt.2010.42.4.244 Case Report Open Access Reversible Proximal Renal Tubular Dysfunction after One-Time Ifosfamide Exposure Young Il Kim, M.D. The alkylating agent ifosfamide is an anti-neoplastic used to treat various pediatric and adult Ju Young Yoon, M.D. malignancies. Its potential urologic toxicities include glomerulopathy, tubulopathy and hemorrhagic cystitis. This report describes a case of proximal renal tubular dysfunction and Jun Eul Hwang, M.D. hemorrhagic cystitis in a 67-year-old male given ifosfamide for epitheloid sarcoma. He was Hyun Jeong Shim, M.D. also receiving an oral hypoglycemic agent for type 2 diabetes mellitus and had a baseline Woo Kyun Bae, M.D. glomerular filtration rate of 51.5 mL/min/1.73 m2. Despite mesna prophylaxis, the patient ex- Sang Hee Cho, M.D. perienced dysuria and gross hematuria after a single course of ifosfamide plus adriamycin. Ik-Joo Chung, M.D. The abrupt renal impairment and serum/urine electrolyte imbalances that ensued were consistent with Fanconi’s syndrome. However, normal renal function and electrolyte status were restored within 14 days, simply through supportive measures. A score of 8 by Naranjo Department of Hematology-Oncology, adverse drug reaction probability scale indicated these complications were most likely Chonnam National University Medical School, Gwangju, Korea treatment-related, although they developed without known predisposing factors. The currently undefined role of diabetic nephropathy in adult ifosfamide nephrotoxicity
    [Show full text]
  • Inherited Tubulopathies of the Kidney Insights from Genetics
    CJASN ePress. Published on April 1, 2020 as doi: 10.2215/CJN.14481119 Inherited Tubulopathies of the Kidney Insights from Genetics Mallory L. Downie ,1,2 Sergio C. Lopez Garcia ,1,2 Robert Kleta,1,2 and Detlef Bockenhauer 1,2 Abstract The kidney tubules provide homeostasis by maintaining the external milieu that is critical for proper cellular function. Without homeostasis, there would be no heartbeat, no muscle movement, no thought, sensation, or emotion. The task is achieved by an orchestra of proteins, directly or indirectly involved in the tubular transport of 1Department of Renal water and solutes. Inherited tubulopathies are characterized by impaired function of one or more of these specific Medicine, University transport molecules. The clinical consequences can range from isolated alterations in the concentration of specific College London, London, United solutes in blood or urine to serious and life-threatening disorders of homeostasis. In this review, we will focus on Kingdom; and genetic aspects of the tubulopathies and how genetic investigations and kidney physiology have crossfertilized each 2Department of other and facilitated the identification of these disorders and their molecular basis. In turn, clinical investigations of Nephrology, Great genetically defined patients have shaped our understanding of kidney physiology. Ormond Street CJASN ccc–ccc Hospital for Children 16: , 2020. doi: https://doi.org/10.2215/CJN.14481119 NHS Foundation Trust, London, United Kingdom Introduction potentially underlying cause through clinical observa- Homeostasis refers to the maintenance of the “milieu tions. It is clinicians, who, together with genetic and Correspondence: Prof. interieur,” which, as expressed by the physiologist physiologic scientists, have often led the discovery of Detlef Bockenhauer, “ Department of Renal Claude Bernard, is a condition for a free and inde- these transport molecules and their encoding genes Medicine, University pendent existence” (1).
    [Show full text]
  • Bartter Syndrome
    Bartter syndrome Author: Dr Giacomo Colussi1 Creation date: August 2001 Update: September 2003, March 2005 Scientific Editor: Dr Adalberto Sessa 1A.O. Ospedale di Circolo e Fondazione Macchi, Viale Borri, 57, 21100 Varese, Italy. Giacomo.Colussi@ospedale.varese.it: Abstract Keywords Disease name and synonyms Excluded diseases Definition Differential diagnosis Clinical description and mechanism Management including treatment Etiology Genetic counseling Antenatal diagnosis Unresolved questions References Abstract Bartter syndrome (BS) is a hereditary condition transmitted as an autosomal recessive (Bartter type 1 to 4) or dominant trait (Bartter type 5). The disease associates hypokalemic alkalosis with varying degrees of hypercalciuria. It is a consequence of abnormal function of the kidneys, which become unable to properly regulate the volume and composition of body fluids due to defective reabsorption of NaCl in a specific structure of the kidney called the " loop of Henle ". A first consequence of the tubular defect in BS is polyuria. Indeed, high urine volume is already present during fetal life, and is responsible for particular complications of pregnancy, i.e. polyhydramnios and premature delivery. Low potassium levels in the blood may result from overactivity of the renin-angiotensin II-aldosterone hormone system that is essential in controlling blood pressure. To date, at least five genes have been linked to BS, and characterize five types of BS. BS type 1 is linked to mutations of the gene SLC12A1 (Solute carrier family 12 sodium/potassium/chloride transporters, member 1) on chromosome 15 (15q15-q21.1). BS type 2 is linked to a gene called KCNJ1 (mapped to chromosome 11q21-25), BS type 3 is linked to the gene ClCNKb (mapped to chromosome 1p36) while BS type 4 is linked to gene BSND (mapped to chromosome 1p31).
    [Show full text]
  • Inherited Tubulopathies of the Kidney Insights from Genetics
    CJASN ePress. Published on April 6, 2020 as doi: 10.2215/CJN.14481119 Inherited Tubulopathies of the Kidney Insights from Genetics Mallory L. Downie ,1,2 Sergio C. Lopez Garcia ,1,2 Robert Kleta,1,2 and Detlef Bockenhauer 1,2 Abstract The kidney tubules provide homeostasis by maintaining the external milieu that is critical for proper cellular function. Without homeostasis, there would be no heartbeat, no muscle movement, no thought, sensation, or emotion. The task is achieved by an orchestra of proteins, directly or indirectly involved in the tubular transport of 1Department of Renal water and solutes. Inherited tubulopathies are characterized by impaired function of one or more of these specific Medicine, University transport molecules. The clinical consequences can range from isolated alterations in the concentration of specific College London, London, United solutes in blood or urine to serious and life-threatening disorders of homeostasis. In this review, we will focus on Kingdom; and genetic aspects of the tubulopathies and how genetic investigations and kidney physiology have crossfertilized each 2Department of other and facilitated the identification of these disorders and their molecular basis. In turn, clinical investigations of Nephrology, Great genetically defined patients have shaped our understanding of kidney physiology. Ormond Street CJASN ccc–ccc Hospital for Children 16: , 2020. doi: https://doi.org/10.2215/CJN.14481119 NHS Foundation Trust, London, United Kingdom Introduction potentially underlying cause through clinical observa- Homeostasis refers to the maintenance of the “milieu tions. It is clinicians, who, together with genetic and Correspondence: Prof. interieur,” which, as expressed by the physiologist physiologic scientists, have often led the discovery of Detlef Bockenhauer, “ Department of Renal Claude Bernard, is a condition for a free and inde- these transport molecules and their encoding genes Medicine, University pendent existence” (1).
    [Show full text]
  • Factors Affecting the Environmentally Induced, Chronic Kidney Disease Of
    environments Review Factors Affecting the Environmentally Induced, Chronic Kidney Disease of Unknown Aetiology in Dry Zonal Regions in Tropical Countries—Novel Findings Sunil J. Wimalawansa 1,* and Chandra B. Dissanayake 2 1 Cardio Metabolic & Endocrine Institute, North Brunswick, NJ 08902, USA 2 Department of Geology, University of Peradeniya, National Institute of Fundamental Studies, Kandy 20000, Sri Lanka; cbdissa@gmail.com * Correspondence: suniljw@hotmail.com Received: 20 November 2019; Accepted: 11 December 2019; Published: 18 December 2019 Abstract: A new form of chronic tubulointerstitial kidney disease (CKD) not related to diabetes or hypertension appeared during the past four decades in several peri-equatorial and predominantly agricultural countries. Commonalities include underground stagnation of drinking water with prolonged contact with rocks, harsh climatic conditions with protracted dry seasons, and rampant poverty and malnutrition. In general, the cause is unknown, and the disease is therefore named CKD of unknown aetiology (CKDu). Since it is likely caused by a combination of factors, a better term would be CKD of multifactorial origin (CKDmfo). Middle-aged malnourished men with more than 10 years of exposure to environmental hazards are the most vulnerable. Over 30 factors have been proposed as causative, including agrochemicals and heavy metals, but none has been properly tested nor proven as causative, and unlikely to be the cause of CKDmfo/CKDu. Conditions such as, having favourable climatic patterns, adequate hydration, and less poverty and malnutrition seem to prevent the disease. With the right in vivo conditions, chemical species such as calcium, phosphate, oxalate, and fluoride form intra-renal nanomineral particles initiating the CKDmfo. This article examines the key potential chemical components causing CKDmfo together with the risk factors and vulnerabilities predisposing individuals to this disease.
    [Show full text]
  • Renal Biopsy: Clinical Correlations November 9, 4:30-6:30 P.M
    Renal Biopsy: Clinical Correlations November 9, 4:30-6:30 p.m. 20 19 Washington, DC Nov. 5–10 ASN Kidney Week 2019 – Renal Biopsy: Clinical Correlations (Full Syllabus) Case 1 from Kammi J. Henriksen, MD – University of Chicago A 50-year-old man with HIV infection (currently with an undetectable viral load), human herpesvirus 8 (HHV-8) infection, Kaposi sarcoma, and multicentric Castleman disease presented with 2 weeks of fatigue, vomiting, and anorexia. He had recently completed a course of trimethoprim and sulfamethoxazole for cellulitis. Notably, he was diagnosed with HIV infection 13 years prior to admission. He was started on highly active antiretroviral therapy (HAART) with a tenofovir-containing regimen 10 years after the diagnosis of HIV. Despite treatment, his CD4 levels remained low (100-200/µL). His HIV infection was complicated by multicentric Castleman disease, which was diagnosed 1 year prior to admission when the patient presented with fever and bilateral axillary adenopathy. Lymph node biopsy at that time showed follicular hyperplasia with HHV-8–positive cells. On admission, physical examination was significant for dry mucous membranes, sinus tachycardia, and a diffuse papular rash over his torso and extremities consistent with Kaposi sarcoma. Workup was significant for severe hyponatremia, AKI, and microscopic hematuria with dysmorphic red blood cells (RBCs). Laboratory findings were as follows: Serum Sodium 103 mEq/L Creatinine 3.7 mg/dL (previous baseline 0.9 mg/dL) HHV-8 33,700 copies/mL IL-6 83.2 pg/mL ANCA Negative Antinuclear antibodies Negative C3/C4 Negative Urine 24-Hour protein 2.1 g Urine sediment microscopy with renal tubular epithelial cells, granular casts, and RBCs.
    [Show full text]