INTRODUCTION

Sarcoidosis (S) is an idiopathic multisystemic granulomatous disorder, histologically characterized by epithelioid non-caseating granulomas involving above all lungs, liver, eyes and skin.

The incidence of renal involvement ranges from 3-23% with a wide spectrum of abnormalities.

("Bergner R - 2003" [1]) and renal failure is observed in 0.7-1% of cases according to the largest studies about S patients (pts) ("Baughman R - 2001" [2], " [3] (full text) James D - 1984" [3] (full text)).

Granulomatous interstitial nephritis (GIN) is the typical renal lesion: it is observed in 20% of cases with kidney S at biopsy ("Bergner R - 2003" [1]) and in 7-23% of autopsies in S pts.

("Ricker W - 1949" [4]; "Longcope W - 1952" [5]). Conversely in Italian renal biopsy registry GIN is found only in 0.5-0.9% of all biopsies, since usually renal S is a silent disease rarely giving acute kidney injury (AKI) and kidney biopsy isn’t performed. In the literature, there are only 100 reported cases of AKI due to sarcoid GIN (sGIN) and only 30% with S limited in the kidneys. Outcome of sGIN-AKI isn’t favorable because >50% pts have chronic kidney disease (CKD) and 7.5% end stage renal disease (ESRD) (" [6]Berliner AR - 2006" [6]).

In Italy S is a rare disease, because its prevalence is below 0.05%. There isn’t a national S registry: in Piemonte and Valle d’Aosta 271 S pts were observed from 2006 to 2011 (Registro interregionale delle malattie rare regioni di Piemonte e Valle d’Aosta).

Our aim was to retrospectively evaluate clinical and therapeutic characteristics of pts with kidney S diagnosed in Italy in the last years.

METHODS

Inclusion criteria: S aspects at renal biopsy, with exclusion of other causes of GIN. 23 pts enrolled (7 females and 16 males) from 16 Italian centres. All pts but 2 (coming from Egypt and Ivory Coast) were Italian. 6 pts had chronic kidney disease (CKD). 19 pts presented sGIN, 4 pts others aspecific lesions (No-sGIN). Mean age: 56.4 years (range 31-76). At presentation, 18 pts presented aspecific symptoms (asthenia 14 pts, fever 7, weight loss 6, itch 2, headache 1); respiratory symptoms were observed in 8 pts (cough in 5 pts, dyspnea 3, thoracic pain 2), gastroenteric  symptoms in 4 pts, ocular symptoms in 4 pts, arthralgia in 3 pts, peripheral lymphadenopathy in 2 pts, erithema nodosum in 1 pt. At presentation 11 pts had lung S (I stage 2 pts, II stage 8 pts, III stage 1 pt) and increased seric angiotensin converting enzyme (sACE) was found in 10 pts (43%): 6 sGIN pts, 4 No-sGIN pts. Noone of No-sGIN pts had normal ACE. There was hypercalcemia in 8 pts (35%), hypercalciuria in 2 pts (9%, both No-sGIN pts). In 21 pts (91%) kidney biopsy got S diagnosis, even in 9 pts with lung disease (4 pts without respiratory symptoms). 6 pts only showed kidney S at diagnosis (all sGIN pts). All pts but one, with nephrosic proteinuria (No-sGIN pt), presented AKI: mean plasmatic (pl) creatinine (creat) was 4 mg/dl and mean 24h-proteinuria 1 g. One patient required haemodialysis in the first weeks because of anuria. All pts received oral corticosteroids (prednisone 0.5-1mg/kg/day) and 8 pts also intravenous pulses of methylprednisolone (MP) (1g for 3 days).

RESULTS

Pts with increased sACE at kidney involvement seemed to present a milder AKI (normal sACE mean maximum (max) pl creat 4.44 mg/dl, increased sACE mean max pl creat 3.66 mg/dl, p = 0.7725).

A complete recovery of renal function (pl creat less than 1.2 mg/dl or basal pl creat value before AKI) was observe in 13 pts(56%) in a mean of  13.7 months (range 6 days – 60 months), while 8 pts (35%) had only a partial recovery (mean pl creat 2.0 mg/dl) in 58.1 months. Corticosteroid therapy lasted 15.3 months on average.  At 1 month follow up all pts’ mean pl creat was 1.8 mg/dl, 24h-proteinuria 0.25 g.

All CKD pts but one had a complete recovery. All No-sGIN pts had a complete recovery. In pt with nephrosic proteinuria, who always maintained normal function, 24h-proteinuria was 0.4 g after 1 month steroids. 1 pt was lost at follow up. No pts progressed toward ESRD. MP intravenous pulses wasn’t associated with better renal function recovery considering 1 month follow up mean pl creat (MP pts 1.85 mg/dl, only oral steroid pts 1.63 mg/dl, p = 0.6950).          

sGIN was associated with more severe AKI:  both groups had similar basal pl creat (sGIN  1.24 mg/dl, No-sGIN 1.00 mg/dl,  p = 0.0519) but different mean max pl creat (sGIN  4.27 mg/dl, No-sGIN 2.25 mg/dl, p = 0.0079) (Figure 3). sGIN pts had a worse recovery of  renal function considering 1 month follow up mean pl creat (sGIN  2.1 mg/dl, No-sGIN 1.00 mg/dl,  p = 0.0004) (Figure 3). This is also evident considering pts only treated with oral prednisone (1 month follow up mean pl creat was 2.13 mg/dl in sGIN, 1.00 mg/dl in No-sGIN, p = 0.0008). Observing pts treated with MP intravenous pulses before oral prednisone, No-sGIN pt had a better 1 month follow up renal function (pl creat 0.9 mg/dl) than sGIN pts (mean pl creat  2.2 mg/dl).

CONCLUSION

In most of our cases renal biopsy got S diagnosis in pts affected by systemic unrecognized disease. sGIN is associated with a more severe AKI and a worse recovery independently of steroid therapy. Increased sACE seems not to be predictive of sGIN (Pearson chi² = 4.56 p = 0.033).            

Corticosteroid therapy seems effective to ameliorate renal function and to arrest progression towards ESRD.