Correspondence
Case 31-2007: A Man with Abdominal Pain and Elevated Creatinine
N Engl J Med 2008; 358:312-313January 17, 2008
- Article
To the Editor:
In the Case Record of a 41-year old man with acute renal failure, discussed by Rabb and Colvin (Oct. 11 issue),1 kidney biopsy revealed lesions that the discussants ascribe to nonsteroidal antiinflammatory drugs in association with dehydration. However, several observations remain unexplained: first, the low platelet count; second, the increased serum levels of lactate dehydrogenase; and third, the severe abdominal pain. Of note, the patient was a visitor from a Western European country. An important differential diagnosis of acute renal failure in Europe is nephropathia epidemica, caused by Puumala virus infection. A hallmark of the disease is its acute onset with chills, fever and malaise, and abdominal pain; patients typically have thrombocytopenia and elevation of lactate dehydrogenase levels in conjunction with elevated serum creatinine levels.2 Proteinuria is transient and can be up in the nephrotic range.3 Histologic changes are unspecific and include features of interstitial nephritis and mild glomerular histologic lesions.4 The clinical course is benign, with complete spontaneous recovery in almost all cases. The history of the patient described in the Case Record is very consistent with Puumala virus infection; serologic testing would be helpful to confirm or rule out the diagnosis.
4 ReferencesChristian S. Haas, M.D.
University Hospital Tuebingen, 72076 Tuebingen, Germany
cs_haas@yahoo.com 1
Case Records of the Massachusetts General Hospital (Case 31-2007). N Engl J Med 2007;357:1531-1541
Full Text | Web of Science | Medline2
Settergren B . Clinical aspects of nephropathia epidemica (Puumala virus infection) in Europe: a review. Scand J Infect Dis 2000;32:125-132
CrossRef | Web of Science | Medline3
Ala-Houhala I ,Koskinen M ,Ahola T , et al. Increased glomerular permeability in patients with nephropathia epidemica caused by Puumala hantavirus. Nephrol Dial Transplant 2002;17:246-252
CrossRef | Web of Science | Medline4
Mustonen J ,Helin H ,Pietila K , et al. Renal biopsy findings and clinicopathologic correlations in nephropathia epidemica. Clin Nephrol 1994;41:121-126
Web of Science | Medline
To the Editor:
The instructive discussion of the Case Record by Rabb and Colvin highlights the inadequacies of current techniques for the early diagnosis of acute kidney injury but fails to highlight recent advances in urinary biomarkers. Our group and others have discovered that proteins emanating from the injured nephron itself may provide the best early biomarkers of acute kidney injury in humans. Neutrophil gelatinase–associated lipocalin (NGAL) is rapidly secreted in the urine in response to ischemia, nephrotoxins, and glomerulonephritides but not in response to prerenal failure from volume depletion. Its appearance in the urine marks the onset of early acute kidney injury with dramatic predictability.1,2 Similarly, interleukin-18 and kidney injury molecule 1 (KIM-1) released into the urine in prompt response to ischemic but not prerenal injury provide early biomarkers of impending acute kidney injury and also predict adverse outcomes.3,4 Remarkably, much of the confusion surrounding the early diagnosis of acute kidney injury and its cause is being eliminated by the adaptive response of the stressed kidney itself. Clinical platforms for the rapid measurement of these novel biomarkers are very close to validation.
Prasad Devarajan, M.D.
Cincinnati Children's Hospital, Cincinnati, OH 45229
prasad.devarajan@cchmc. org Chirag Parikh, M.D., Ph.D.
Yale University, New Haven, CT 06520Jonathan Barasch, M.D., Ph.D.
Columbia University, New York, NY 10032Drs. Devarajan and Barasch report that Abbott Diagnostics has signed an exclusive licensing agreement with Cincinnati Children's Hospital and Columbia University for developing urinary NGAL as a biomarker of acute renal failure. No other potential conflict of interest relevant to this letter was reported.
4 References1
Mishra J ,Dent C ,Tarabishi R , et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 2005;365:1231-1238
CrossRef | Web of Science | Medline2
Brunner HI ,Mueller M ,Rutherford C , et al. Urinary neutrophil gelatinase-associated lipocalin as a biomarker of nephritis in childhood-onset systemic lupus erythematosus. Arthritis Rheum 2006;54:2577-2584
CrossRef | Web of Science | Medline3
Parikh CR ,Abraham E ,Ancukiewicz M ,Edelstein CL . Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit. J Am Soc Nephrol 2005;16:3046-3052
CrossRef | Web of Science | Medline4
Liangos O ,Perianayagam MC ,Vaidya VS , et al. Urinary N-acetyl-beta-(D)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure. J Am Soc Nephrol 2007;18:904-912
CrossRef | Web of Science | Medline
To the Editor:
An alternative analysis of this case would be acute pancreatitis as the initial illness, which would account for the abdominal pain, nausea, vomiting, and elevated lipase. This could have caused dehydration and, in turn, renal-vein thrombosis, which is generally associated with marked proteinuria and D-dimer elevation. Acute renal failure with tubular necrosis could have followed. Computed tomography or magnetic resonance imaging of the abdomen would have aided in this diagnosis. Renal-vein thrombosis may gradually recanalize without treatment, resulting in the restoration of renal function.
Francis J. Kleeman, M.D.
Southern Maine Medical Center, Biddeford, ME 04005Author/Editor Response
Haas brings up the possibility that a hantavirus, Puumala virus, was the cause of this patient's syndrome. Hantavirus was one of the etiologic agents discussed as being capable of causing the patient's abdominal pain, low platelet count, hematuria, and proteinuria, particularly because the patient was a traveler from Western Europe, although we have no evidence of contact with rodents. The renal biopsy showed focal hemorrhage and a relatively sparse inflammatory infiltrate, findings that are compatible with this diagnosis but certainly not specific for it. Serologic testing for hantaviruses was not performed.
Devarajan and colleagues state that the discussion of the clinical differential diagnosis “fails to highlight recent advances in urinary biomarkers.” We agree that this is an important topic, and the discussion highlights “the recent development of new urinary biomarkers” and provides references to some of the same biomarkers they discuss. However, it is premature at this time, on the basis of the available data, to replace urinary microscopy or other common techniques in routine clinical practice with any of the new candidate serum or urinary biomarkers. There is currently a great opportunity for both the discovery of novel serum and urinary biomarkers of acute kidney injury and validation of the long list of current candidates.1-3
Kleeman suggests that acute pancreatitis and secondary renal-vein thrombosis with spontaneous recanalization could account for the acute tubular necrosis, proteinuria, and spontaneous resolution in this case. Though this is possible, it is less likely. Nevertheless, this suggestion highlights a common problem, since many cases of acute tubular necrosis are multifactorial in origin, and it is difficult to accurately pinpoint the initial cause or all the additive insults. In addition, it was commonly thought that patients who survived an episode of acute kidney injury due to either acute tubular necrosis or another process would regain full renal function with structural resolution. However, increasing evidence points to deleterious long-term consequences of even a single episode of acute kidney injury.4,5
5 ReferencesHamid Rabb, M.D.
Johns Hopkins Hospital, Baltimore, MD 21287Robert B. Colvin, M.D.
Massachusetts General Hospital, Boston, MA 021141
Hewitt SM ,Dear J ,Star RA . Discovery of protein biomarkers for renal diseases. J Am Soc Nephrol 2004;15:1677-1689
CrossRef | Web of Science | Medline2
Shah SH ,Mehta RL . Acute kidney injury in critical care: time for a paradigm shift? Curr Opin Nephrol Hypertens 2006;15:561-565
CrossRef | Web of Science | Medline3
Bonventre JV . Diagnosis of acute kidney injury: from classic parameters to new biomarkers. Contrib Nephrol 2007;156:213-219
CrossRef | Web of Science | Medline4
Basile DP ,Donohoe D ,Roethe K ,Osborn JL . Renal ischemic injury results in permanent damage to peritubular capillaries and influences long-term function. Am J Physiol Renal Physiol 2001;281:F887-F899
Web of Science | Medline5
Burne-Taney MJ ,Yokota N ,Rabb H . Persistent renal and extrarenal immune changes after severe ischemic injury. Kidney Int 2005;67:1002-1009
CrossRef | Web of Science | Medline
- Citing Articles (9)
Citing Articles
1
Robert Wagner, Ursel Leicht-Biener, István Mucsi, Karlheinz Seitz. (2012) Ibuprofen or diclofenac is associated with more severe acute kidney injury in nephropathia epidemica. Scandinavian Journal of Urology and Nephrology 46:1, 65-69
CrossRef2
Prasad Devarajan. (2011) Biomarkers for the early detection of acute kidney injury. Current Opinion in Pediatrics 23:2, 194-200
CrossRef3
N. Braun, M. Kimmel, M.D. Alscher, U. Helmchen, J. Velden. (2011) Hantavirusinduzierte Nephropathia epidemica. Der Nephrologe 6:1, 57-59
CrossRef4
PRASAD DEVARAJAN. (2010) Review: Neutrophil gelatinase-associated lipocalin: A troponin-like biomarker for human acute kidney injury. Nephrology 15:4, 419-428
CrossRef5
Prasad Devarajan. (2010) Neutrophil gelatinase-associated lipocalin: a promising biomarker for human acute kidney injury. Biomarkers in Medicine 4:2, 265-280
CrossRef6
Prasad Devarajan. (2008) NGAL in Acute Kidney Injury: From Serendipity to Utility. American Journal of Kidney Diseases 52:3, 395-399
CrossRef7
Prasad Devarajan. (2008) The Future of Pediatric Acute Kidney Injury Management—Biomarkers. Seminars in Nephrology 28:5, 493-498
CrossRef8
Mark M. Mitsnefes, Philip R. Khoury, Prasad Devarajan. (2008) Beware of subgroup analysis. Pediatric Nephrology 23:7, 1191-1192
CrossRef9
Prasad Devarajan. (2008) Emerging urinary biomarkers in the diagnosis of acute kidney injury. Expert Opinion on Medical Diagnostics 2:4, 387-398
CrossRef
