C- 03: TIN in systemic diseases
H-15: Recurrence of initial nephropathy
Sarcoidosis in Native and Transplanted Kidneys: Incidence,
Pathologic Findings, and Clinical Course.
Bagnasco SM, Gottipati S, Kraus E, Alachkar N, Montgomery RA, et al.
PLoS ONE 2014; 9(10): e110778. doi:10.1371/journal.pone.0110778
ABSTRACT
Renal involvement by sarcoidosis in native and transplanted kidneys classically presents as
non caseating granulomatous interstitial nephritis. However, the incidence of sarcoidosis in
native and transplant kidney biopsies, its frequency as a cause of end stage renal disease
and its recurrence in renal allograft are not well defined, which prompted this study. The
electronic medical records and the pathology findings in native and transplant kidney
biopsies reviewed at the Johns Hopkins Hospital from 1/1/2000 to 6/30/2011 were searched.
A total of 51 patients with a diagnosis of sarcoidosis and renal abnormalities requiring a
native kidney biopsy were identified. Granulomatous interstitial nephritis, consistent with
renal sarcoidosis was identified in kidney biopsies from 19 of these subjects (37%). This is
equivalent to a frequency of 0.18% of this diagnosis in a total of 10,023 biopsies from native
kidney reviewed at our institution. Follow-up information was available in 10 patients with
biopsy-proven renal sarcoidosis: 6 responded to treatment with prednisone, one progressed
to end stage renal disease. Renal sarcoidosis was the primary cause of end stage renal
disease in only 2 out of 2,331 transplants performed. Only one biopsy-proven recurrence of
sarcoidosis granulomatous interstitial nephritis was identified.
Conclusions
Renal involvement by sarcoidosis in the form of granulomatous interstitial nephritis was a
rare finding in biopsies from native kidneys reviewed at our center, and was found to be a
rare cause of end stage renal disease. However, our observations indicate that recurrence of
sarcoid granulomatous inflammation may occur in the transplanted kidney of patients with
sarcoidosis as the original kidney disease.
The study was approved by the John Hopkins Institutional Review Board (protocol
NA_0000114
COMMENTS
Sarcoidosis is a systemic disorder of unclear etiology, which results from an abnormal cellmediated immune reaction, and is characterized by non caseating granulomatous
inflammation with epithelioid cells and multinucleated giant cells. Sarcoidosis affects
individuals mostly in their third or fourth decades. Its incidence has been reported to be as
high as 40 cases per 100,000 in Europe.
Sarcoidosis most commonly affects the lungs, but multiple organs such as the central
nervous system, liver, heart, skin, and kidney can be involved.
Only a few cases of recurrent sarcoidosis with granulomatous inflammation in the
transplanted kidney have been described.
A total of 14,306 kidney biopsies were reviewed in the Department of Pathology at the Johns
Hopkins Hospital between January 2000 to June 2011, of which 10,023 were from native
kidneys, and 4,283 from kidney allografts.
A diagnosis of sarcoidosis was reported in the medical history of 52 patients who had
renal/urinary abnormalities requiring native or allograft kidney biopsy, with a total of 57
kidney biopsies performed on these subjects.
Main histological diagnoses in 56 native kidney biopsies from 51 patients carrying a
diagnosis of sarcoidosis.
Interstitial nephritis was the main diagnosis in approximately half of these patients (27 cases,
granulomatous and non granulomatous), the remaining patients showed renal lesions without
no obvious association with sarcoidosis.
The 19 patients with a biopsy-proven granulomatous sarcoidosis in the native kidney had
abnormal serum creatinine: 3.96±2.35 mg/dl (average ± SD; range 1.9–9 mg/dl). Proteinuria
was known to be present in 12 patients, ranging from trace to 2.5 g/24 hours, it was
quantified in 8 patients with an average of 0.94±0.65 g/24 hours. Hypercalcemia was present
in 7 of 19 patients but only 3 had evidence of microcalcifications in the kidney biopsy.
A clinical history of systemic sarcoidosis was recorded for 4 kidney transplant recipients. All
had inactive disease at the time of transplantation. Two had previous history of lung
sarcoidosis, but the cause of ESRD was hypertensive nephrosclerosis. Only two patients
(one black female, and one white female) had sarcoidosis in lung and kidney, and lost their
native kidneys due to renal sarcoidosis. This suggests that the frequency of sarcoidosis as
primary cause of renal failure leading to ESRD could be estimated as less than 1 in 1000 in
patients who received a transplanted kidney.
This study indicates that less than 1% of patients with renal abnormalities requiring a native
kidney biopsy have a clinical history of sarcoidosis. These observations on kidney biopsies
suggest that in patients with history of sarcoidosis and renal dysfunction about one third
shows pathologic manifestation of renal involvement by sarcoidosis as interstitial nephritis
with granulomatous inflammation. Although renal involvement by sarcoid granulomatous
interstitial nephritis is a rare primary cause of ESRD in transplant recipients, it can recur in
the renal allograft.
Pr. Jacques CHANARD
Professor of Nephrology