Dürr, Daniel

Frey, Felix J.

Klein, Maja

Nitsch, Dorothea

Serra, Andreas L.

Wermuth, Bendicht

RERO DOC Digital Library

We present a case of a 39-year-old woman with polycystickidney disease who started peritoneal dialysis in 2000. Fouryears later, the patient received a cadaver donor transplantfrom a 52-year-old woman. Surgery was performed withouttechnical difﬁculties and good initial graft perfusion wasobserved. An immunosuppressive regimen consisting oftacrolimus, mycophenolate mofetil and steroids was initiated.The post-operative course showed persistent anuriawith dependency on dialysis every 48 h. Isotopic renogramdemonstrated a vascular pattern with an almost ﬂat excretioncurve. Renal biopsy showed broad ischaemic necrosis ofthe tissue sample.Detailed screening for thrombosis risk factors revealedincreased prothrombin immunoreactivity and moleculargenetic analysis identiﬁed a heterozygous point mutationat position 20210 of the prothrombin gene.Recently, a clinical study reported the potential forinherited hypercoagulability due to the V Leiden factoror prothrombin G20210A, to predispose to acute graftthrombosis [1].The G20210A prothrombin mutation occurs in 1–2% ofthe population and represents a frequent cause of inheritedthrombophilia.Our patient developed RCN in the early post-transplantperiod. Organ transport, storage and transplantationproblems and haemodynamic instability or rejection inthe early post-transplant period were ruled out. Only theG20210A mutation of the prothrombin gene was found.The G20210A prothrombin mutation is a risk factor forgraft loss and is linked to a high frequency of acute vascularrejection due to the broad antigen exposure triggeredby vascular wall injury and induced by the prothromboticstate [1,2].The ﬁrst case series of patients heterozygous for theG20210A prothrombin mutation and unsuccessful kidneytransplantation was published in 1999 and included threerenal transplant recipients who experienced graft loss dueto thrombosis in the peri-operative period [3]. The G20210Amutation is also associated with a 2.95-fold increased riskfor allograft loss, an observation that provides the basisfor screening recipients before renal transplantation [4].In contrast, screening of 562 transplant recipients founda prevalence of 2% and no signiﬁcant differences werereported in the 30 day and 1 year graft survival rates amongpatients with or without the G20210A mutation [5].It seems reasonable to believe that endothelial injuryand ischaemic-reperfusion syndrome were related to trans-plantation in a woman with no previous history ofthrombophilia, but with a heterozygous point mutation atposition 20210 of the prothrombin gene, could trigger RCN.New research is required to elucidate the role of thismutation in the course of kidney transplantation.Conﬂict of interest statement. None declared.1Hospital ClinicDepartment of Nephrologyand Renal Transplantation2Hospital ClinicDepartment of Haemotherapyand HaemostasisBarcelonaSpainEmail: 36008lqp@comb.esLuis F. Quintana1Federic Cofan1Juan C. Reverte´2Federic Oppenheimer1Josep M. Campistol11. Irish A. Hypercoagulability in renal transplant recipients.Identifying patients at risk of renal allograft thrombosis andevaluating strategies for prevention. Am J Cardiovasc Drugs2004; 4: 139–1492. Heidenreich S, Junker R, Wolters H et al. Outcome of kidneytransplantation in patients with inherited thrombophilia: dataof a prospective study. J Am Soc Nephrol 2003; 14: 234–2393. Oh J, Schaefer F, Veldmann A et al. Heterozygousprothrombin gene mutation: a new risk factor for earlyrenal allograft thrombosis. Transplantation 1999; 68: 575–5784. Fischereder M, Schneeberger H, Lohse P et al. Increasedrate of renal transplant failure in patients with the G20210Amutation of the prothrombin gene. Am J Kidney Dis 2001;38: 1061.45. Pherwani AD, Winter PC, McNamee PT et al. Is screening forfactor V Leiden and prothrombin G20210A mutations in renaltransplantation worthwhile? Results of a large single-centerU.K. study. Transplantation 2003; 76: 603–605doi:10.1093/ndt/gﬁ341Advance Access publication 19 December 2005A puzzling case of high serum creatininein a healthy womanSir,A 42-year-old woman with a history of recurrent urinarytract infection presented to the emergency room with acutemalaise and abdominal pain. On physical examination,the patient was febrile and the right kidney was painful onpercussion. Blood tests showed moderate leukocytosis,high C-reactive protein (>200mg/l) and a serum creatinineand serum urea in the normal range. A dipstick analysis ofthe urine revealed leukocyturia and bacteriuria and theabdominal ultrasound showed normal kidneys. An acutepyelonephritis was diagnosed and after a 3-day course ofintravenous antibiotics the patient was discharged afebrileand in good condition with a prescription of levoﬂoxacin foranother 7 days.Ten days later, the patient was seen by the generalpractitioner. At that time, the patient appeared healthy withnormal body temperature and an unremarkable abdominalexamination. Surprisingly, the serum creatinine was consider-ably elevated (400mmol/l; normal range: 45–102 mmol/l).The blood test was repeated by a second general practitionerand conﬁrmed the previous results. A computerized tomo-graphy scan of the abdomen was performed and revealedno pathological ﬁndings. Acute renal failure was suspectedand the patient was admitted to our hospital for furtherexamination. The physical examination was still unremark-able (i.e. no signs of uraemia). The blood tests were repeatedand serum creatinine (82 mmol/l) and serum urea (3.3mmol/l;normal range: 2–8mmol/l) values were in the normal range.How can the highly pathological serum creatininemeasured by both general practitioners in this obviouslyhealthy woman be explained? The general practitionersused the enzymatic method (Reﬂotron Creatinine; RocheDiagnostics, Switzerland) for serum creatinine analysis,whereas the Jaffe´ method was applied in our hospital.In the enzymatic assay, the non-proteinogenic amino acidsarcosine is formed in the course of the reaction (Table 1).Sarcosine, an intermediary of one-carbon metabolism, isusually undetectable in human blood and, therefore, doesnot interfere with the test. To support the diagnosis ofsarcosinaemia, the patient’s serum creatinine level wasmeasured on a single blood sample level using both theenzymatic and the Jaffe´ method simultaneously. The serum1456 Nephrol Dial Transplant (2006) 21: 1456 The Author [2005.] Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.For Permissions, please email: journals.permissions@oxfordjournals.orgcreatinine level was 403mmol/l (enzymatic method) and79 mmol/l (Jaffe´ method), respectively. The diagnosis wasconﬁrmed in our patient by an amino acid analysis (HPLCion-exchange chromatography) that revealed substantialsarcosinaemia of 460 mmol/l. The high concentration ofsarcosine interfered with the enzymatic test method usedby the practitioners.Sarcosinaemia is caused by a deﬁciency of sarcosinedehydrogenase [1] and was originally described in 1966in a brother and sister with mild mental retardation [2].Later on, newborn screening programmes revealed thatthis inherited defect of amino acid metabolism occursin about 1:350 000 (New England) and reﬂects mainlya benign metabolic state [3]. The gene for human sarcosinedehydrogenase is localized on chromosome 9q34 andgenetic data are consistent with an autosomal recessivemode of inheritance.The Jaffe´ method is known to be rather unspeciﬁcand to interfere with a number of compounds, but notwith sarcosine. Thus, in the presence of sarcosinaemia, theserum creatinine concentration is more accurately determinedby the not speciﬁc Jaffe´ than by the speciﬁc enzymaticmethod.Conﬂict of interest statement. None declared.1Clinic for NephrologyUniversity Hospital, Zurich2Department of Nephrologyand HypertensionUniversity Hospital, Berne3General Practitioner, Heimberg4Department for Laboratory MedicineUniversity Hospital, Berne, SwitzerlandEmail: andreas.serra@usz.chAndreas L. Serra1Maja Klein2Dorothea Nitsch2Daniel Du¨rr3Bendicht Wermuth4Felix J. Frey21. Eschenbrenner M, Jorns MS. Cloning and mapping of thecDNA for human sarcosine dehydrogenase, a ﬂavoenzymedefective in patients with sarcosinemia. Genomics 1999; 59:300–3082. Gerritsen T, Waisman HA. Hypersarcosinemia: an inborn errorof metabolism. N Engl J Med 1966; 275: 66–693. Levy HL, Coulombe JT, Benjamin R. Massachusetts MetabolicDisorders Screening Program: III. Sarcosinemia. Pediatrics1984; 74: 509–513doi:10.1093/ndt/gﬁ343Table 1. The Reﬂotron creatinine assaySubstrates Enzymes ProductsCreatinineþH2O !Creatinine iminohydrolaseN-MethylhydantoineþNH3N-Methylhydantoineþ 2H2OþATP !NMethylhydantoine amidohydrolaseN-CarbamoylsarcosineþADPþPN-CarbamoylsarcosineþH2O !NCarbamoylsarcosine amidohydrolaseSarcosineþCO2þNH3SarcosineþH2OþO2 !Sarcosine oxidase GlycineþHCHOþH2O2H2O2þ indicator !Peroxidase DyeþH2ONephrol Dial Transplant (2006) 21: 1457 1457

A puzzling case of high serum creatinine in a healthy woman

Abstract

Similar works

Full text

Available Versions

RERO DOC Digital Library