**4. Obstructive nephropathy**

Abnormal calcium metabolism is a well known feature of sarcoidosis. Hypercalcemia and hypercalcuria is related to endogenous vitamin D. It is suggested that excess vitamin D may result in increased intestinal calcium absorption and consequent hypercalcemia, hypercalcuria and renal calculi. Hypercalcuria is defined as using excretion of 300 mg/day in men or 250 mg/day in women, about 2-5% healthy adults exhibit hypercalcuria. Hypercalcuria is the most common renal manifestation. It is caused by glomerular filtration of excess blood calcium and suppression by high calcitriol levels on PTH activity. It affects 50% of patients with sarcoidosis, often with an insidious onset because most patients remain normocalcemic. Sharma suggests that 10% of patients with sarcoidosis are diagnosed with hypercalcemia whereas 30% of patients with sarcoidosis show an increase in serum calcium. (Sharma, 1996)

In 1988, Foster described eight patients where he described extra uveitis may be the presenting sign of sarcoidosis. It was the first study that suggested that there may be unexpected presenting signs of sarcoidosis. (Foster, 1988) One of these symptoms may be nephrolithiasis. In a study from Italy, the charts 618 patients with histologically proven sarcoidosis was reviewed in 1978-92 in order to identify nephrolithiasis as a presenting feature of sarcoidosis. (Rizzato et al 1995) The authors concluded that calculi were the presenting feature of sarcoidosis in 6 out of 618 patients (1%) and was the first manifestation of disease in 14 (2. 2%) of the patients. In another 9 patients who presented with pulmonary involvement, persistent hematuria or pyuria led to discovery of stones via ultrasound or intravenous pyelography. Given that this is an uncommon disease, there is a very small chance that a physician seeing a patient for the first time with a new kidney stone will later prove to be is sarcoidosis. In the literature, the overall prevalence of nephrolithiasis is 10% in patients with sarcoidosis. (Muther et al 1981 and Rizzato 1995) The incidence of 2.2% exceeds more than 20 times the expected yearly rate of renal calculi in the general population (36 per 100, 000 in women and 123 in men in Rochester (Johnson et al 1979), 122 in California (Hiatt et al 1982) and 68 in Kyoto –Osaka. (Yoshida and Okada, 1990) In course of chronic sarcoidosis, approximately 10-13.8% of patients have at least 1 asymptomatic stone. (Lebacq, 1970)

Treatment of hypercalcuria involves minimization of dietary calcium and Vitamin D, avoidance of UV exposure, and dietary oxalate restriction. This is because an increase in intestinal calcium absorption caused by excess in 1, 25 dihydroxyvitamin D may result in an increase in urinary oxalate excretion especially if diet is low in calcium. Overabsorption of calcium leaves less of this divalent cation to complex with oxalate in the proximal intestine so more oxalate is delivered to the colon in which anion is hyperabsorbed. Corticosteriods

Hypercalcemia may cause decrease glomerular filtration rate by vasoconstricting the afferent arterioles and thereby decreasing renal blood flow (Berliner et al 2006). Additionally, it may cause tubular necrosis, tubulointerstitial non-granulomatous inflammation with calcium deposits ultimately causing nephrocalcinosis and chronic kidney disease (Berliner et al 2006). Hypercalciuria, which is three times as more common as hypercalcemia, predisposes patients to calcium oxalate nephrolithiasis, which may ultimately lead to obstruction or chronic pyelonephritis (Berliner et al 2006 and Sharma 1996). Renovascular complications as well as

Abnormal calcium metabolism is a well known feature of sarcoidosis. Hypercalcemia and hypercalcuria is related to endogenous vitamin D. It is suggested that excess vitamin D may result in increased intestinal calcium absorption and consequent hypercalcemia, hypercalcuria and renal calculi. Hypercalcuria is defined as using excretion of 300 mg/day in men or 250 mg/day in women, about 2-5% healthy adults exhibit hypercalcuria. Hypercalcuria is the most common renal manifestation. It is caused by glomerular filtration of excess blood calcium and suppression by high calcitriol levels on PTH activity. It affects 50% of patients with sarcoidosis, often with an insidious onset because most patients remain normocalcemic. Sharma suggests that 10% of patients with sarcoidosis are diagnosed with hypercalcemia whereas 30% of patients with sarcoidosis show an increase in serum calcium.

In 1988, Foster described eight patients where he described extra uveitis may be the presenting sign of sarcoidosis. It was the first study that suggested that there may be unexpected presenting signs of sarcoidosis. (Foster, 1988) One of these symptoms may be nephrolithiasis. In a study from Italy, the charts 618 patients with histologically proven sarcoidosis was reviewed in 1978-92 in order to identify nephrolithiasis as a presenting feature of sarcoidosis. (Rizzato et al 1995) The authors concluded that calculi were the presenting feature of sarcoidosis in 6 out of 618 patients (1%) and was the first manifestation of disease in 14 (2. 2%) of the patients. In another 9 patients who presented with pulmonary involvement, persistent hematuria or pyuria led to discovery of stones via ultrasound or intravenous pyelography. Given that this is an uncommon disease, there is a very small chance that a physician seeing a patient for the first time with a new kidney stone will later prove to be is sarcoidosis. In the literature, the overall prevalence of nephrolithiasis is 10% in patients with sarcoidosis. (Muther et al 1981 and Rizzato 1995) The incidence of 2.2% exceeds more than 20 times the expected yearly rate of renal calculi in the general population (36 per 100, 000 in women and 123 in men in Rochester (Johnson et al 1979), 122 in California (Hiatt et al 1982) and 68 in Kyoto –Osaka. (Yoshida and Okada, 1990) In course of chronic sarcoidosis, approximately 10-13.8% of patients have at least 1 asymptomatic

Treatment of hypercalcuria involves minimization of dietary calcium and Vitamin D, avoidance of UV exposure, and dietary oxalate restriction. This is because an increase in intestinal calcium absorption caused by excess in 1, 25 dihydroxyvitamin D may result in an increase in urinary oxalate excretion especially if diet is low in calcium. Overabsorption of calcium leaves less of this divalent cation to complex with oxalate in the proximal intestine so more oxalate is delivered to the colon in which anion is hyperabsorbed. Corticosteriods

obstructive nephropathy will also be further discussed subsequently.

**4. Obstructive nephropathy** 

(Sharma, 1996)

stone. (Lebacq, 1970)

are usually necessary to normalize these parameters as they can decrease inflammatory activity and reduce calcitriol syntheses.

Retroperitoneal lymph nodes can enlarge sufficiently to cause urethral obstruction.

(Frailly et al 1990). Sarcoidosis has also been shown to be responsible for bilateral hydronephrosis on the basis of retroperitoneal lymph node enlargement, with resolution after corticosteroid treatment. (Miyazaki 1995).
