Renal involvement is a common finding in the diagnosis of multiple myeloma, where nearly 30–40 % of patients were found to have raised serum creatinine levels [1]. Myeloma can damage the kidney at multiple levels: namely glomerular, tubular and interstitial. Two major causes of renal insufficiency in patients with myeloma are light chain cast nephropathy and hypercalcemia. Apart from that, renal insufficiency occurs due to light chain (AL) amyloidosis, light chain deposition disease, interstitial nephritis or could be drug-induced. However, in rare occasions, monoclonal heavy chain deposition and non-monoclonal protein related renal injury may also occur [2].
Out of the various renal manifestations of myeloma, renal tubular acidosis is an uncommon entity. Although adult proximal tubular dysfunction is well described as an association of myeloma; distal renal tubular acidosis (dRTA) in the background of multiple myeloma is extremely rare. It is described only in few reports in literature. Proximal tubules are affected during the process where the filtered light chains get reabsorbed and catalyzed within the epithelial cells. These epithelial cells get damaged with the activation of lysosomal enzymes and from direct toxicity of light chains [3–5]. Distal tubules are thought to be affected due to either hypercalciuria or hypergammaglobulinaemia (usually polyclonal) [6, 7].
Among the case series of RTA with multiple myeloma, DeFronzo et al [8] described in his series of 14 patients with urinary acidification defects: two had distal tubular involvement. Another Czech case series showed that eight out of 21 patients developed distal renal tubular defects [9]. Out of the three case reports which described the association of dRTA and myeloma, first case report, described a patient having early myeloma with IgG lambda chains who developed distal RTA [5] and second, a patient with Sjogrens’ syndrome subsequently developed monoclonal gammopathy of unknown significance (MGUS) with dRTA [10]. Third report described a patient with IgA kappa multiple myeloma with both proximal and distal renal tubular involvement, probably due to the overflow of light chains from proximal to the distal renal tubules and deposition in the renal tubular epithelial cells [11]. But the pathogenesis of dRTA was unclear in the above case reports as they neither had hypercalciuria nor polyclonal hypergammaglobulinaemia. But they had monoclonal gammaglobulinaemia which may have caused dRTA in the same mechanism in which polyclonal hypergammaglobulinaemia caused dRTA.
In our patient, the diagnosis of dRTA was made by the presence of hypokalemia, hyperchloremic metabolic acidosis with high urinary pH above 5.5. Distal tubular involvement was confirmed by the presence of low fractionated bicarbonate excretion and its association with bilateral nephrolithiasis or nephrocalcinosis [11]. There was no proximal tubular involvement in our patient. It is mandatory to find a secondary cause for dRTA, since concomitant treatment of RTA and the underlying cause is important for a better prognosis [12]. Therefore, we searched for a cause for the dRTA in our patient, in the background of anaemia and high ESR. Autoimmune panel, ionized calcium levels, CT scan of chest and abdomen, transaminases and other screening for granulomatous diseases were all negative. But, investigation of bone marrow and serum protein electrophoresis led to the diagnosis of multiple myeloma. Immunofixation showed a monoclonal peak (36.7 g/l) which could be the cause for dRTA. Unfortunately, free light chain assay was not readily available, hence urine immunofixation was performed and it showed absent overt light chain excretion.
Pathogenesis of isolated dRTA due to myeloma is not well described earlier. It is highly unlikely that light chain deposition would cause to dRTA, as it’s known to cause proximal RTA. Previous studies have demonstrated an association between hypergammaglobulinemia and distal RTA [8, 13]. But the hypergammaglobulinamia, which is associated with dRTA, is usually polyclonal [14]. Feringa et al have described a case of Waldenstrom’s Macroglobulinaemia, in which IgM monoclonal hyperglobulinaemia associated with dRTA [14]. Therefore, in the absence of hypercalciuria in our patient, multiple myeloma induced monoclonal hypergammaglobulinaemia would have led to dRTA. Unfortunately, renal biopsy has not been performed on her, so that the exact pathogenesis was difficult to ascertain.
Distal RTA can lead to bilateral nephrolithiasis due to hypercalciuria, hyperphosphaturia, hypocitraturia, and low urine pH. In the absence of hypercalciuria, hyperphosphaturia, hypocitraturia, we assumed that urine pH has led to the extensive stone formation in our patient [15].
Having arrived at the diagnosis of dRTA, we started her on oral bicarbonate and oral potassium chloride. Her lower limb weakness showed a marked improvement with the normalization of potassium. Subsequently, with correction of acidosis we could tail off potassium supplementation. After obtaining Oncology opinion, standard chemotherapy was initiated as the treatment for myeloma and at 3 months of completion of chemotherapy, her bicarbonate requirement and the inflammatory markers were noted to be reduced and the monoclonal band peak also reduced to 7.2 g/l. In our attempt of managing this patient, we assume that the treatment of myeloma can improve the monoclonal gammopathy as well as the RTA.
