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American Journal of Kidney Diseases

Quiz Page December 2011

An Unusual Cause of Renal Colic
  • Giorgina Barbara Piccoli
    Correspondence
    Address correspondence to Giorgina B. Piccoli, MD, SS Nephrology Azienda Ospedaliera Universitaria san Luigi Gonzaga, Department of Clinical and Biological Sciences, Ospedale san Luigi, Regione Gonzole 10, Orbassano, University of Torino, Italy
    Affiliations
    SS Nephrology, Azienda Ospedaliera Universitaria san Luigi Gonzaga, Department of Clinical and Biological Sciences, Ospedale san Luigi, Orbassano, University of Torino, Italy
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  • Agostino De Pascale
    Affiliations
    Radiology, Azienda Ospedaliera Universitaria san Luigi Gonzaga, Department of Clinical and Biological Sciences, Ospedale san Luigi, Orbassano, University of Torino, Italy
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  • Francesco Porpiglia
    Affiliations
    Urology, Azienda Ospedaliera Universitaria san Luigi Gonzaga, Department of Clinical and Biological Sciences, Ospedale san Luigi, Orbassano, University of Torino, Italy
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  • Andrea Veltri
    Affiliations
    Radiology, Azienda Ospedaliera Universitaria san Luigi Gonzaga, Department of Clinical and Biological Sciences, Ospedale san Luigi, Orbassano, University of Torino, Italy
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      Clinical Presentation

      A 38-year-old woman was referred for metabolic evaluation of multiple kidney stones. Her clinical history was uneventful until her first pregnancy 4 years previously, when she developed a malar rash with positive antinuclear antibodies. After delivery, she developed profound muscle weakness requiring urgent medical advice. She was found to have severe hypokalemia with a serum potassium level of 2.1 mEq/L (2.1 mmol/L) and elevated creatine kinase (5,633 U/L) and myoglobin levels (7,880 ng/mL).
      The patient was hospitalized, and her condition slowly improved with potassium supplementation. Nephrology workup showed mild proteinuria (protein excretion, 0.3-1 g/d), normal kidney function, metabolic acidosis (pH 7.32; bicarbonate, 18-20 mEq/L [18-20 mmol/L]), and urinary alkalosis (pH 7.5 in the absence of urinary tract infections). With potassium citrate supplementation, potassium levels stabilized (3.2-3.7 mEq/L [3.2-3.7 mmol/L]). Serologic testing showed positive antinuclear, anti-SSA/Ro, and anti-SSB/La antibodies. Anti-DNA antibody, complement, Schirmer test, and salivary ultrasound results were unremarkable. Ultrasound of the kidneys was normal, with no evident stones. She was discharged with a diagnosis of tubulointerstitial nephropathy and undefined collagen disease. Subsequently, the patient discontinued follow-up until 4 years later, when recurrent urinary tract infections, intermittent joint pain, and renal colic prompted her to seek medical advice again. The computed tomographic (CT) scan is shown in Figure 1, Figure 2.
      Figure thumbnail gr1
      Figure 1Computed tomographic scan shows bilateral kidney stones in almost all calyces.
      Figure thumbnail gr2
      Figure 2Three-dimensional reconstruction of the kidney stones that almost precisely reproduce the morphology of the calyces.
      ■ What is the cause of this patient's renal colic?
      ■ What processes result in this CT finding?
      ■ What is this patient's diagnosis?
      ■ What other kidney diseases is this patient at risk of?

      Discussion

      What is the cause of this patient's renal colic?

      The CT scan identifies staghorn calculi in almost all calyces of both kidneys. Staghorn calculi are branched usually infected stones that often show rapid growth. Involvement of at least 2 calyces is required for defining a stone as “staghorn” (Fig 1). Presenting symptoms often include upper urinary tract infection and sepsis. Renal colic is comparably rare because the stones are large and usually retained in the upper urinary tract. Not infrequently, kidney failure is the first sign of large staghorn stones.
      • Evan A.P.
      • Lingeman J.
      • Coe F.
      • et al.
      Renal histopathology of stone-forming patients with distal renal tubular acidosis.

      What processes result in this CT finding?

      Although virtually every type of stone may form staghorn calculi, 75%-90% of them share a struvite matrix, usually combined with carbonate apatite. Struvite stones are formed in the presence of high urine pH and urinary tract infections, typically with urease-producing bacteria such as Proteus, Ureaplasma, and Klebsiella species.
      Our patient underwent surgical removal of the major stones, and analysis revealed calcium oxalate monohydrate (47%), carbonate apatite (20%), and struvite (30%). Carbonate apatite is typical of stones formed in distal renal tubular acidosis.

      What is this patient's diagnosis?

      The patient developed kidney stones secondary to distal renal tubular acidosis in Sjögren syndrome.
      • Evan A.P.
      • Lingeman J.
      • Coe F.
      • et al.
      Renal histopathology of stone-forming patients with distal renal tubular acidosis.
      • Shearn M.A.
      • Tu W.H.
      Latent tubular acidosis in Sjögren's syndrome.
      • Bae E.H.
      • Han C.W.
      • Lee J.H.
      • et al.
      Hypokalemia associated with nephrocalcinosis Distal renal tubular acidosis associated with Sjögren's syndrome.
      • Pessler F.
      • Emery H.
      • Dai L.
      • et al.
      The spectrum of renal tubular acidosis in paediatric Sjögren syndrome.
      The diagnosis of Sjögren syndrome is mainly clinical, supported by nonspecific laboratory evidence of autoimmune derangements. In milder or slowly progressive cases, the classic hallmarks (positive Schirmer test result and atrophy of the salivary glands) may not be evident at presentation. The full-blown syndrome may take years to develop, and the diagnosis of “undefined collagen disease” often is made initially.
      • Evan A.P.
      • Lingeman J.
      • Coe F.
      • et al.
      Renal histopathology of stone-forming patients with distal renal tubular acidosis.
      • DuBose Jr, T.D.
      A 42 year old woman with flaccid paralysis.
      The dissociation among disease markers may avert attention from the associated renal tubular disorders. Increasingly recognized as common, these apparently ancillary elements should point to Sjögren syndrome.
      • Pessler F.
      • Emery H.
      • Dai L.
      • et al.
      The spectrum of renal tubular acidosis in paediatric Sjögren syndrome.
      • DuBose Jr, T.D.
      A 42 year old woman with flaccid paralysis.
      • Devuyst O.
      • Lemaire M.
      • Mohebbi N.
      • Wagner C.A.
      Autoantibodies against intercalated cells in Sjögren syndrome [letter].
      Described in the late 1960s, the relationship between distal renal tubular acidosis (type I) and Sjögren syndrome was almost forgotten until recently reported as a cause of electrolyte imbalance in children and of nephrocalcinosis and stone disease in adults,
      • Shearn M.A.
      • Tu W.H.
      Latent tubular acidosis in Sjögren's syndrome.
      as seen in our patient (Fig 3). Presentation with flaccid paralysis caused by profound hypokalemia occasionally has been described.
      • DuBose Jr, T.D.
      A 42 year old woman with flaccid paralysis.
      The mechanism by which Sjögren syndrome leads to renal tubular acidosis is incompletely understood. In a few cases, complete absence of the adenosine triphosphatase proton pump (H+-ATPase) responsible for distal proton secretion could be shown in the intercalated cells of the collecting ducts.
      • Shearn M.A.
      • Tu W.H.
      Latent tubular acidosis in Sjögren's syndrome.
      The relationship with specific antibodies targeting intercalated cells also may explain the abrupt onset of symptoms and occasional remissions.
      • Devuyst O.
      • Lemaire M.
      • Mohebbi N.
      • Wagner C.A.
      Autoantibodies against intercalated cells in Sjögren syndrome [letter].
      Figure thumbnail gr3
      Figure 3In this computed tomographic image, large and multiple staghorn stones are evident; the presence of minute peripapillary intraparenchymal calcifications identifies a combined picture of nephrocalcinosis/stone disease.
      In our patient, Schirmer test has now turned positive and atrophy of the salivary glands is present. She continues to have metabolic acidosis (pH 7.31; bicarbonate, 18 mEq/L [18 mmol/L]) and low-normal potassium (3.5 mEq/L [3.5 mmol/L]), normal serum and urinary calcium (10 mg/dL [2.5 mmol/L]; 22.5 mg/24 h [5.6 mmol/24 h], respectively), and low urinary citrate levels (0.6 mmol/24 h). Urinalysis shows pH 7.5, proteinuria with protein excretion of 100 mg/dL, and microhematuria in the absence of urinary tract infection. The presence of relatively high urinary pH in the setting of metabolic acidosis and absence of urinary tract infections indicates distal renal tubular acidosis.

      What other kidney diseases is this patient at risk of?

      Due to a lack of uniform diagnostic criteria, the prevalence of Sjögren syndrome is a matter of discussion. Furthermore, the different criteria for performing kidney biopsy may affect the reported prevalence of various kidney diseases. Nevertheless, the prevalence of tubulointerstitial nephropathy has been estimated to be as high as 25% in patients with Sjögren syndrome and presently is considered the most frequent form of kidney involvement.
      • Bae E.H.
      • Han C.W.
      • Lee J.H.
      • et al.
      Hypokalemia associated with nephrocalcinosis Distal renal tubular acidosis associated with Sjögren's syndrome.
      • Maripuri S.
      • Grande J.P.
      • Osborn T.G.
      • et al.
      Renal involvement in primary Sjögren's syndrome: a clinicopathologic study.
      Recent data suggest that steroids may be effective in slowing the progression of tubulointerstitial nephropathy and may lead to widening the biopsy policy on when to perform biopsy in tubulointerstitial disorders.
      • Maripuri S.
      • Grande J.P.
      • Osborn T.G.
      • et al.
      Renal involvement in primary Sjögren's syndrome: a clinicopathologic study.
      As in other complex autoimmune diseases, almost all types of glomerular diseases have been described, including membranoproliferative cryoglobulinemic glomerulonephritis and focal segmental glomerulosclerosis. Interstitial and glomerular involvement may coexist.
      • Kaufman I.
      • Schwartz D.
      • Caspi D.
      • Paran D.
      Sjögren's syndrome—not just sicca: renal involvement in Sjögren's syndrome.

      Final Diagnosis

      Staghorn renal calculi and nephrocalcinosis secondary to distal renal tubular acidosis in Sjögren syndrome.

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