Sarcoidosis is a multisystemic autoinflammatory disease of unknown cause that can affect the kidney in a small but clinically significant percentage of cases.1,2 Its main renal manifestations include granulomatous or non-granulomatous interstitial nephritis, calcium metabolism disorders, and glomerulonephritis (typically membranous, but also membranoproliferative or focal segmental). More rarely, it can cause vascular involvement (granulomatous angiitis, thrombotic microangiopathy, vasculitis). It may also present as a proximal tubulopathy (Fanconi syndrome) or distal tubulopathy (nephrogenic diabetes insipidus and renal tubular acidosis). We present a case of sarcoidosis with renal involvement manifesting as significant hypophosphatemia in the setting of an incomplete Fanconi syndrome.

A 56-year-old Caucasian male, a crane operator, smoker, with a personal history of mixed dyslipidemia, class 1 obesity, and past hepatitis B virus (HBV) infection, presented in 2015 with constitutional syndrome (asthenia, anorexia, lower extremity weakness). Laboratory testing revealed hypercalcemia with hypercalciuria, suppressed intact PTH (iPTH), elevated angiotensin-converting enzyme (ACE), and impaired kidney function (sCr 2.9 mg/dl, eGFR 24 ml/min). Further workup with chest CT identified numerous mediastinal lymphadenopathies, and abdominal CT revealed left ureteral calcium oxalate monohydrate nephrolithiasis causing obstructive uropathy. Serum protein electrophoresis was normal, QuantiFERON was negative, PTHrP was within the normal range, 25-OH vitamin D3 was low (19.2 ng/mL, reference range > 20) without 1,25-dihydroxyvitamin D3 measurement, and pulmonary function tests were normal. The patient was treated with hemodynamic support, and laser lithotripsy was performed along with placement of a double-J ureteral stent. His general condition improved, and calcium levels normalized rapidly over the following weeks, with parallel improvement of kidney function. Fine-needle aspiration (FNA) of a mediastinal lymph node was inconclusive; therefore, a diagnosis of probable sarcoidosis with pulmonary and renal involvement was made, and specific treatment was deferred.

The patient maintained good general condition with progressive improvement in glomerular filtration rate up to CKD stage G3aA1 (Fig. 1), but slowly and progressively developed hypophosphatemia, reaching nadir values of 1.9 mg/dl, requiring oral phosphate supplementation. Subsequent investigations demonstrated borderline elevated FGF 23 levels (192 U/ml, reference range < 180), normal urinary sediment, markedly elevated phosphaturia with decreased tubular reabsorption of phosphate (TRP), and generalized aminoaciduria (Fig. 1). There was no associated hypouricemia, glycosuria, or metabolic acidosis; fractional excretion of uric acid (FE UA) was normal, and PTH was within the normal range after calcium normalization, with no evidence of concomitant primary hyperparathyroidism (PHPT). Genetic testing for tubulopathies was negative. A diagnosis of incomplete Fanconi syndrome was established, and kidney biopsy was proposed, which the patient repeatedly declined. Given the absence of systemic disease activity, PET-CT was not performed. The patient maintains good general condition, normocalcemia, moderate hypophosphatemia, and continues treatment with oral phosphate supplementation. His ACE levels decreased during the first week of treatment and have remained normal throughout these 10 years of follow-up.

Fig. 1.

Analytical evolution from the beginning of follow-up.

Hypophosphatemia in sarcoidosis is present in 14% of cases,3 and the main causes are proximal tubulopathy and coexisting primary hyperparathyroidism.3,4 The pathogenesis is related to proximal tubulopathy, which induces phosphaturia, and secondarily to increased calcitriol synthesis, which enhances intestinal calcium and phosphorus absorption, triggering a counterregulatory increase in FGF 23 along with increased tubular sensitivity to PTH, thereby further increasing phosphaturia.

Four cases of Fanconi syndrome in sarcoidosis have been described in the literature,5–7 and their main characteristics are summarized in Table 1. Their renal functional prognosis is favorable with corticosteroid treatment.

Spontaneous remission is common (50% overall, 70% within the initial two to five years after diagnosis),8,9 but in 30% of cases the disease becomes chronic (10–25% severe disease).10

In our case, the favorable functional course of the patient motivated the decision not to initiate corticosteroid treatment, and the insidious development of hypophosphatemia delayed the diagnosis over time. All of this underscores the need to carefully analyze calcium-phosphorus metabolism abnormalities in patients with sarcoidosis, with the aim of optimizing therapies that minimize the long-term secondary effects of these sustained internal milieu disturbances.