Renal Papillary Necrosis-A Sixteen-Year Clinical 1 Matthew D. Griffin, Erik J. Bergstralh, and Timothy S. Larson2 emphasizes that continued recognition of papillary M.D. Griffin, IS. Larson. Division of Nephrology and necrosis will necessitate an awareness of its clinical Internal Medicine. Mayo Clinic and Mayo Foundation. spectrum in the context of current diagnostic and Rochester, MN therapeutic practice. E.J. Bergstralh. Section of Biostatistics, Mayo Clinic and Key Words: Diabetes mellitus. analgesic abuse, urinary tract Mayo Foundation. Rochester. MN infection, urinan, tract obstruction, sickle cell disease (J. Am. Soc. Nephrol. 1995; 6:248-256) R enal papillary necrosis (RPN) is a term used to describe a particular form of renal damage in ABSTRACT which any or all of the papillae undergo selective This study sought to characterize patients with renal necrosis in a manner that can be clearly demonstrated papillary necrosis seen at one tertiary referral center radiologically or histologically. The clinical syndromes by reviewing medical records of patients with a con- that have been described as accompanying this pro- cess include acute fulminant renal failure, obstruc- firmed diagnosis between January 1 , 1976 and Sep- tion by a sloughed papilla, hematuria, and loin pain, tember 1 , 1992. One hundred sixty-five cases were passage of tissue in the urine, recurrent or severe identified. The mean age at diagnosis was 57 yr (SD urinary tract infection (UT!), and chronic renal failure 15). The female-to-male ratio was 1 .1 :1 .0. Ninety-two (1-8). percent of patients were white. Seventy-seven percent From its first clear description by Friedreich in 1877 of cases were unsuspected before diagnosis, and in association with benign prostatic obstruction (9), 16% were diagnosed at autopsy. The most common accepted relationships have been established between associated conditions were urinary tract infection, RPN and diabetes mellitus, excessive use of analgesic analgesic abuse, urinary tract obstruction, diabetes mixtures, sickle cell disease, and urinary obstruction (6,9-12). The role ofUTI as an independent risk factor mellitus, and sickle cell disease. There was consider- remains unclear, but It is undoubtedly a frequent able overlap in the presence ofthese conditions, with accompaniment ( 1 ,8, 13, 14). Individual reports and two or more identified in 36% of patients. In addition, small collections of cases have suggested associations 1 1 % of patients had none of these well-recognized between RPN and a number of other conditions (15- risks. Other diagnoses in this group included lupus 19). nephritis, Wegener’s granulomatosis, and renal artery The currently available literature on the clinical stenosis. A decline in case numbers of approximately spectrum of RPN draws heavily from autopsy studies 50% was demonstrated over the last 10 yr studied. This (20-24), small groups ofcases from single institutions period was associated with a 57% reduction in the (2,3,25,26), and studies confined to radiologically or number of excretory urograms carried out, suggest- surgically diagnosed cases (27-29). Only a few series ing that changes in diagnostic imaging preference have previously included large numbers of patients or a full clinical spectrum ( 1 ,8,30). Moreover, there are may have contributed. Vital status and renal out- no recent studies of RPN to define the relevance of this come data after diagnosis were obtained in 93% of lesion in modern medical practice, the prognosis over cases. Of those diagnosed while living, survival was a prolonged period from the time of diagnosis, and the lowest among diabetic patients. Ten-year survival for trends that may have occurred in the past two de- nondiabetics was not significantly different from the cades. We therefore sought to described the charac- expected survival of an age- and sex-matched co- teristics of RPN at a single, large, tertiary referral hort. The overall risk for requiring renal replacement center over the past 1 6 yr and observe trends and therapy after the diagnosis of renal papillary necrosis outcome during this period of time. in surviving patients was low (7% of 136 patients at METHODS risk). Diabetes was the only factor associated with an increased risk of end-stage renal failure. This study Chart Review By use ofthe Mayo Clinic’s unique medical records system, a computerized search was made of all patient visits regis- r Received November 22, 1994. Accepted February 8, 1995. tened between January 1976 and September 1992 for diag- 2 Correspondence to Dr. IS. Larson, Division of Nephrology and Internal Med noses of “renal papillary necrosis” on equivalent terms. The clne. Mayo Clinic. 200 FIrst Street, SW, Rochester, MN 55905. chart of each patient identified was reviewed. A radiologic 1046.6673/0602-0248$03.00/0 Journal of the American Society of Nephrology diagnosis was accepted if excretory urognaphy (EXU), netno- CopyrIght C 1995 by the American society of Nephrology grade unognaphy, or both were reported by a consultant 248 Volume 6 - Number 2 ‘ 1995 Griffin et a) radiologist at our institution as showing “changes of renal Follow-Up papillary necrosis” or “definite renal papillary necrosis. “ Re- An attempt was made to obtain outcome data through ports of ultrasound and computed tomognaphic (CT) scans March 1993 on all patients. Questionnaires were sent out to were also reviewed when available-in no case was a diagno- those without adequate chart information on or after this sis of RPN made for the first time by these imaging modali- date, and phone contact was attempted with nonnesponders ties. Cases with reports stating “possible” on “probable renal after 2 months. papillary necrosis” were not included in the absence of other definite diagnostic evidence. Pathologic diagnosis was ac- Statistical Analysis cepted if examination of passed tissue, a surgical specimen, on autopsy by a consultant pathologist at our institution was Data were analyzed with the SAS software package (SAS reported as showing RPN. Cases with pathologic or radiologic Institute, Cary, NC). Survival curves were constructed by use diagnosis from other Institutions without subsequent review of the Kaplan-Meien method for the overall group and for of diagnostic material at Mayo Clinic were also excluded. Of selected subgroups. An expected survival curve was con- 229 charts reviewed, 165 met the above criteria. Along with structed on the basis of an age- and sex-matched cohort basic patient characteristics, details of diagnostic proce- drawn from the 1980 Minnesota life tables. Survival free of dunes, relevant laboratory studies, additional medical condi- end-stage renal failure was also estimated by the Kaplan- lions, nadiologic and histologic reports, and available fol- Meier method. Differences in survival between groups were low-up were recorded. compared by use ofthe log-rank test. Characteristics of those Data for analgesic abuse were accepted if a clear history of with Type I versus Type II diabetes were compared with prolonged heavy use of analgesic mixtures, aspirin on phen- Wilcoxon rank sum on tests as appropriate. All tests were acetin alone, on nonstenoidal anti-inflammatory drugs was two sided with a significance level of 0.05. documented with a compatible clinical picture. Obstruction was accepted if structural or functional urinary tract ob- RESULTS stnuction (not due to a sloughed papilla) was clearly docu- The characteristics of the 165 patients who met our mented. UTI was based on the presence of positive urine criteria for RPN are shown in Table 1 . The patients culture at on within 1 month of diagnosis. Details regarding prior single or recurrent pyelonephnitis on simple urinary were predominantly of the white race (92. 1%), with a infections were also recorded when available. Sickle cell small female predominance overall. The diagnosis was disease was accepted with hemoglobin S levels diagnostic of suspected before radiographic or histologic diagnosis the hetenozygous on homozygous state. of RPN in less than one-quarter (23.0%) of patients TABLE 1. Characteristics of overall group with RPN as well as subgroups with major associated conditions and a group with rare associations or no identified association#{176} Urinary Sickle Overall Analgesic Diabetes Other Characteristic UTI Tract Cell Group Abuse Mellitus Cases Obstruction Disease N (% Total Cases) 165 67 (40.6) 59 (35.7) 48 (29.1) 37 (22.4) 5 (3.0) 18 (10.9) Age (yr) (mean ± SD) 57 ± 15.2 60 ± 15.5 55 ± 13.8 58 ± 16.0 56 ± 16.0 53 ± 13.7 51 ± 16.4 F:M 1.1:1 1.9:1 1.6:1 1:1.3 1.5:1 1:1.5 1:1.3 White 92 94 97 94 89 0 90 Suspicion Before 23.0 19.4 37.2 8.3 27.0 40.0 11.1 Diagnosis Diagnostic EXU 57.6 46.3 84.7 33.3 48.6 100 61.1 Diagnostic RU 15.8 11.9 16.9 16.7 27.0 0 11.1 Tissue Passed 4.2 13.4 3.5 0 16.2 0 0 Surgical Specimen 12.7 13.4 5.1 33.3 8.1 0 16.7 Autopsy Diagnosis 15.8 29.9 0 20.8 13.5 0 16.7 Bilateral RPN 63.0 68.7 79.7 45.8 51.4 100 33.3 Sepsis 15.8 26.9 1.7 18.8 21.6 0 16.7 Hypertension 43.0 38.8 49.2 33.3 51 .4 60.0 38.9 History of TCC 6. 1 3.0 1.7 14.6 5.4 0 11.1 History of Nephrolithiasis 27.2 22.4 32.2 45.8 27.2 0 27.7 Serum Creatinine at 230 ± 274 248 ± 221 195 ± 230 230 ± 204 266 ± 266 106 ± 18 230 ± 504 Diagnosis (mean ± SD In mol/Lb) Normal Serum 24.8 16.4 25.4 12.5 24.3 20.0 55.6 Creatinine at Diagnosis a Note: Subgroups for the five major risk factors are not mutually exclusive because combinations were common.