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Crystalline Light Chain Proximal Tubulopathy and Podocyto- Pathy: a Case Report Tubulopatia Proximal E Podocitopatia De Cadeias Leves Cristalinas: Relato De Caso

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Crystalline Light Chain Proximal Tubulopathy and Podocyto- Pathy: a Case Report Tubulopatia Proximal E Podocitopatia De Cadeias Leves Cristalinas: Relato De Caso CLINICOPATHOLOGICAL CASE | CASO CLÍNICO-PATOLÓGICO Crystalline light chain proximal tubulopathy and podocyto- pathy: a case report Tubulopatia proximal e podocitopatia de cadeias leves cristalinas: relato de caso Authors CASE PRESENTATION A renal ultrasound showed a right kidney Ankit B. Patel1 of 11.9 cm with mild fullness of collect- 1 In this case report we present a 64-year- John Y. Choi ing system and a left kidney of 10.4 cm 2 old man with a history of IgG kappa para- Walter P. Mutter with no signs of hydronephrosis. A bone Astrid Weins3 proteinemia for 14 years with no signs of marrow biopsy 1.5 years prior to presen- Leonardo V. Riella1 multiple myeloma or plasmacytoma who tation showed findings consistent with presented to the renal clinic with new on- a plasma cell dyscrasia but did not meet set hypokalemia and increase in serum 1 Harvard Medical School, Renal criteria for myeloma. Plasma cells were creatinine. His past medical history was Division, Brigham & Women’s 5% without lymphoid infiltrates. Flow Hospital, Boston, MA, EUA. remarkable for a diagnosis of necrobiotic 2 cytometry showed abnormal plasma cells Harvard Medical School, Renal xanthogranuloma for 30 years treated with Division, Newton Wellesley that were kappa restricted. Cytogenetics multiple modalities including chlorambucil, Hospital, Boston, MA, EUA. were normal. 3 Harvard Medical School, thalidomide, cryotherapy, intravenous im- Brigham & Women’s Hospital, munoglobulin, and electron beam therapy. Department of Pathology, Boston, DIFFERENTIAL DIAGNOSIS MA, EUA. He also had a history of squamous cell car- cinoma, melanoma, bilateral carotid artery A middle age patient presented with new- disease, coronary artery disease, and hyper- onset renal dysfunction, worsening albu- tension. He had no fevers, cough, dyspnea, minuria, and increased urinary frequency abdominal pain, nausea, or vomiting but and thirst. His evaluation was notable for did complain of a worsening headache over a urinalysis with no blood but urine total the last week. He also reported increased protein/creatinine of 2.94 g/g and urine urinary frequency and thirst but denied albumin/creatinine of 1.68 g/g. The new any dysuria or hematuria. His medications onset of proteinuria along with renal dys- included aspirin, clopidogrel, amlodipine, function helped guide the differential diag- carvedilol, hydralazine, and atorvastatin. nosis for acute kidney injury. Proteinuria He started no new medications and report- generally is categorized as tubular or ed no sick contacts. His blood pressure was glomerular in origin. Given the history 152/82 mmHg. On physical examination, of paraproteinemia, the new increase in the patient appeared comfortable with a proteinuria could result from an increase clear oropharynx, cardiac exam with regu- in the paraprotein burden. Given the lar rate and rhythm and no murmurs, rubs, modest level of free light chains and that or gallops, clear lung sounds, soft and non- more than half of the total protein found tender abdomen, no lower extremity ede- in the urine was albumin, the proteinuria ma, and numerous erythematous plaques was not due to increased urinary free light chains but rather glomerular in origin. Submitted on: 04/30/2019. on his trunk and extremities. His initial labs Approved on: 08/23/2019. at presentation are summarized in Table 1. The paraprotein can cause glomerular in- Of note, his creatinine was 1.0 mg/dL 10 jury leading to albuminuria. Proteinuria can also be associated with proximal tu- Correspondence to: months prior. Urine sediment examina- Leonardo V. Riella. tion showed occasional epithelial cells and bule dysfunction, which is considered low E-mail: [email protected] white blood cells as well as hyaline casts. molecular weight proteinuria and there is DOI: 10.1590/2175-8239-JBN-2019-0086 99 A chain of crystals TABLE 1 INITIAL LABORATORY VALUES Variable Reference Range Lab value Blood Sodium (mmol/L) 137-146 139 Potassium (mmol/L) 3.5-5.3 3.2 Chloride (mmol/L) 98-107 96 Carbon dioxide (mmol/L) 23-32 27 Urea nitrogen (mg/dL) 5-25 21 Creatinine (mg/dL) 0.6-1.4 1.69 Glucose (mg/dL) 70-100 120 Calcium (mg/dL) 8.6-10.3 8.9 Albumin (g/dL) 4.0-5.0 3.1 Phosphorous (mg/dL) 2.7-4.5 3.2 Magnesium (mg/dL) 1.3-2.7 1. 7 Uric Acid (mg/dL) 2.6-6.0 5.6 Aspartate aminotransferase (U/L) 6-40 30 Alanine aminotransferase (U/L) 10-49 18 Alkaline phosphatase (U/L) 35-130 76 Total Bilirubin (mg/dL) 0-1.0 0.4 Hemoglobin (g/dL) 12.0-17.0 11. 6 Hematocrit (%) 35.0-50.0 35.2 White-cell count (per mm3) 4,500-11,000 8,900 Platelet count (per mm3) 150,000-400,000 265,000 Kappa light chains (mg/dL) 3.3-19.4 48.7 Lambda light chains (mg/dL) 5.7-26.3 1.53 Free Kappa/lambda ratio 0.26-1.65 31.9 M-spike, SPEP (g/dL) None 1.19 IgG Kappa Urine Urinalysis Blood Negative Negative Glucose Negative Negative Protein Negative ++ Specific gravity 1.000-1.035 1. 011 pH 5.0-8.0 7. 0 Sediment Red blood cell (/hpf) 0-3 2 White blood cell (/hpf) 0-4 1 Casts Negative Negative Crystals Negative Negative Chemistry Spot urine protein/creatinine (g/g) < 0.15 2.94 Spot urine microalbumin/creatinine (g/g) 0-0.03 1.68 Urine potassium/Cr (mEq/g) 0-14 49.7 Urine M spike (mg/24hr) None 244 IgG Kappa Urine total protein (g/24hrs) < 0.08 2.2 Braz. J. Nephrol. (J. Bras. Nefrol.) 2020;42(1):99-105 100 A chain of crystals a larger difference between urinary total protein and monoclonal gammopathy (MG) was categorized into albumin excretion. Although tubular injury can lead monoclonal gammopathy of unknown significance to albuminuria, it is not typically to the degree not- (MGUS), smoldering multiple myeloma (SMM), and ed in this case. The patient had a significant cancer multiple myeloma (MM) based on: 1) monoclonal history, although no new treatment during the time protein quantification on protein electrophoresis, 2) course of the renal dysfunction and no signs of recur- monoclonal plasma cell percentage on bone marrow rence of skin cancer. Of note, he did have new onset biopsy, and 3) evidence of end organ damage such as hypokalemia with urine chemistry suggestive of po- renal failure. While this system offered some useful tassium wasting and a known underlying IgG kappa insight on risk stratification and prognosis, a signifi- paraproteinemia. cant proportion of MGUS population developed pro- gressive renal disease. This observation added a new HYPOKALEMIA category to the previous classification: monoclonal Hypokalemia is uncommonly associated with acute gammopathy of renal significance (MGRS)1. A study kidney injury. To determine the etiology of hypoka- conducted between January 2000 and August 2016 lemia, it is important to first identify if there is a de- found 44 of 2,935 MGUS patients during that time crease in potassium intake, an increase in potassium were diagnosed with MGRS suggesting up to 1.5% of output, or a transcellular shift of potassium. The el- MGUS patients have renal complications attributed evated spot urinary potassium/creatinine ratio in this to their monoclonal gammopathy2. MGRS is further patient prior to potassium supplementation suggested categorized based on the presence and type of orga- increase urinary potassium excretion as the etiology nized deposits (Figure 1). If organized deposits are of hypokalemia. Urinary potassium wasting can result detected, the histopathology can be diagnosed based from a number of different causes including: 1) genet- on the shapes and sizes on the deposits. Fibrillary de- ic defects in tubular sodium reabsorption increasing posits are usually 7-12 nm; immunotactoids are 17- distal sodium delivery, a key regulator of potassium 52 nm hollow centered microtubules; and crystalline excretion, 2) hypomagnesemia, which decreases tonic can present with various sizes and shapes usually in inhibition of secretory potassium channels, 3) varied rhomboid or needle form. forms of hyperaldosteronism leading to upregulation of sodium and potassium conductances in the con- HISTOPATHOLOGY necting tubule and collecting duct, or 4) increase in LIGHT MICROSCOPY (LM) urinary anions (e.g. bicarbonate) that are excreted A kidney biopsy was completed for further evalu- with countercations such as potassium to maintain ation. Figure 2a shows Periodic Acid Schiff (PAS) electroneutrality. Hypokalemia with acute kidney stained kidney section with three glomeruli with injury is a unique feature of leptospirosis, however, varied degrees of chronic changes: one glomerulus there was no recent travel or other clinical signs to is globally sclerosed, another glomerulus shows fea- suggest infection. Given the history of paraprotein- tures of collapsing glomerulopathy, and the third emia and high urinary pH, proximal tubule dysfunc- glomerulus has mild mesangial expansion. There are tion with proximal renal tubular acidosis (pRTA) some interspersed normal appearing tubules, some was suspected since it may lead to bicarbonate uri- hypertrophic with obvious PAS-positive protein reab- nary wasting and associated hypokalemia. Proximal sorption granules in the cytoplasm along with basal tubulopathy from paraproteinemia is often associat- nuclei (yellow arrow), while adjacent tubules reveal ed with global proximal tubule dysfunction (Fanconi PAS-negative lacy cytoplasm (blue arrow) (Figure 2c). syndrome). However, this patient had normal serum Figure 2b shows a higher magnification of a glomeru- levels of phosphorus and uric acid with no evidence lus with collapsing features, including extensive pro- of glucosuria indicating that some functions of the tein reabsorption granules in multiple epithelial cells proximal tubule remain preserved. and a collapsed tuft. MONOCLONAL GAMMOPATHY WITH RENAL DISEASE IMMUNOFLUORESCENCE (IF) Monoclonal paraproteins can have an array of dif- Figure 3a and b shows an IF stain on paraffin sections ferent effects on the kidney.
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