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Abstract How to cite this article: Introduction 
Nephrogenic diabetes insipidus (NDI) is characterized by a urinary concentration defect that results from the diminished effectiveness of vasopressin [antidiuretic hormone (ADH)] in the distal nephron.[1] This reflects a resistance to the action of ADH because of disrupted function or regulation of aquaporin-2 channel in the luminal membrane of principal cells. Diagnosis of NDI requires a failure of desmopressin (DDAVP) to cause a rise in urine osmolality (Uosm) to a value that is higher than plasma osmolality (Posm).[2] Acquired NDI is the predominant form of the disease in adults, and most of them have partial instead of complete resistance to ADH. Common causes include treatment with lithium, hypercalcemia, and obstructive uropathy.[2] Autoimmune diseases, especially Sjogren syndrome, have been previously associated with with NDI.[3] In the case of systemic lupus erythematosus (SLE), tubulointerstitial abnormalities like renal tubular acidosis (RTA) can be present,[4],[5],[6] however, NDI is extremely rare, with just a few cases reported so far.[7],[8],[9]
Here, we report the case of a patient fulfilling diagnostic criteria of SLE and antiphospholipid syndrome (APL), that presented partial NDI and distal RTA (dRTA) as cardinal kidney manifestations.
Case Report A 39-year-old woman presented at the emergency department with severe abdominal pain, nausea, and incoercible vomiting. Her past medical history was unremarkable. Four months earlier, she began her symptoms with a sudden appearance of periorbital edema, chemosis, diplopia, and decreased visual acuity; three months later, she presented pain on extraocular movement and sixth nerve palsy was treated symptomatically with no improvement. One month before hospital admission, she exhibited severe epigastric pain nonresponsive to pain relievers, accompanied by abdominal distension and oral feeding intolerance. Her vital signs were as follows: blood pressure 119/74 mm Hg, pulse rate 126/min, respiratory rate 26/min, and body temperature, 36.6°C. In the physical examination she had sixth nerve palsy, increased abdominal girth with tenderness, and decreased peristalsis, without another abnormal findings, including polyuria.
The initial images obtained (computed tomography scan) of the chest and abdomen revealed right subclavian and superior vena cava thrombosis, pleural and pericardial effusion, dilated loops of jejunum and ileum with wall thickening and ascites. Laboratory analysis yielded the following data: Hemoglobin 13.5 g/dL, white blood cell 3980/μL, with 2840 neutrophils and 770 lymphocytes, platelet count 300,000/μL, sodium 161 mEq/L, potassium 3.2 mEq/L, chloride 136.4 mEq/L, urea 30 mg/dL, creatinine 0.75 mg/dL; albumin 2.4 g/dL, lactate dehydrogenase 653 U/L, erythrocyte sedimentation rate 48 mm/h, C-reactive protein 6.63 mg/dL. Other laboratory tests were within normal limits.
Regarding the approach of her sodium disorder, we detected the presence of hypernatremia with consequent elevated Posm but with inappropriately low Uosm and elevated electrolyte-free water clearance (EFWC). Although the patient did not present with polyuria, diabetes insipidus was suspected, so we proceeded to perform a DDAVP test, whose response is shown in [Table 1]. In our patient, the initial Uosm was 223.2 mOsm/kg; after the application of DDAVP, the Uosm increased to 308 mOsm/kg, with gradual improvement of hypernatremia and EFWC, which confirmed the diagnosis of partial NDI. She did not require a second dose of DDAVP.
Furthermore, we detected hyperchloremic metabolic acidosis with normal anion gap (venous blood gas analysis: pH 7.31, pCO2 32.2 mm Hg, pO2 33.2 mm Hg, HCO3 16.8 mmol/L, anion gap 7.8), linking with the urinalysis that showed elevated urine anion gap (41) and pH 5, also suggests the presence of dRTA. The rest of the analysis showed a density of 1.010, and active urine sediment [proteinuria 75 mg/dL, 34–36 leukocytes/high power field (HPF) and 10 erythrocytes/HPF].
Owing to the presence of unprovoked coagulopathy, polyserositis and intestinal activity, we then requested an antibody profile that went as follows: antinuclear antibodies positive 1:640, dsDNA titer 46.6 UI/mL (normal <26.9), lupus anticoagulant 1.46 (normal <1.2), anti-beta-2-glycoprotein I IgM 18.2 (normal <15), anticardiolipin antibodies were negative, anti-SSA and SSB was absent. She had decreased C3 and C4 – C3: 31 mg/dL (normal 90–180); C4: 2.9 mg/dL (normal 10– 40) and positive direct Coombs’ test. Confirming the diagnosis of SLE fulfilling the 2019 criteria from the American College of Rheumatology and the European League Against Rheumatism with an initial SLE Disease Activity Index score of 18 points along with APL. But also exposing the rare presence of two entities, as is the partial NDI and dRTA, both associated with the diagnosis of SLE immunologic activity. She was treated successfully with three intravenous (IV) pulses of methylprednisolone and IV immunoglobulin with a great clinical response.
The authors obtained all appropriate consent forms from the patient for the publication of this case report.
Discussion The present case has the clinical and biochemical behavior of two of the most unusual entities of renal SLE activity. The hallmark of DI is an inability of the kidney to concentrate the urine due to a diminished secretion of ADH or kidney resistance to its action. In general, DI occurring as a manifestation of SLE is exceedingly rare. Central DI (CDI) has been reported as a feature of neurolupus secondary to hypophysitis or associated with vasopressin cell antibodies.[10] In that particular case, the main problem is the complete lack of ADH, but; on the other hand, if the patient shows resistance to the effect of the ADH (in the absence of primary polydipsia, which our patient does not meet criteria), it is considered to be nephrogenic. This asseveration is sustained considering the behavior of Uosm; in this particular case, it was suspected by an inappropriate response of Uosm in the context of hypernatremia, and then confirmed by the observation of a limited concentration response of about 34.5% after the DDAVP test, as the Uosm rose from 223.2 mOsm/kg to 308.7 mOsm/kg.
In complete NDI, an absence or minimal response in Uosm with the administration of DDVAP is expected. However, partial defects are frequent in adults with NDI. Although partial CDI and NDI have a similar response to diagnostic administration of DDVAP, partial NDI tends to have a small increase in Uosm (approximately up to 45%), but remains characteristically low (below 300 mOsm/L).[11] It is remarkable that our patient showed sustained improvement despite not administering a second dose of DDAVP. It is not clear yet if the maintained response of the patient was because of the DDAVP test itself or a sensitizing effect achieved by glucocorticoid administration upregulating vasopressin receptors.[12]
To our knowledge, only few cases of NDI have been reported.[7],[8],[9] All of them presented in young women with coexisting Sjogren syndrome, simultaneous clinical manifestations of autoimmunity and biochemical data compatible with a urinary concentration defect. Tubulointerstitial lesions are frequent in patients with SLE. There is a direct relationship between lupus glomerulonephritis and histopathological findings in the tubules and interstitium, with more severe findings found in class IV nephritis.[4] The severity of interstitial inflammation correlates with the degree of renal inflammation and is an accurate prognostic factor of deterioration of renal function.[5]
dRTA is frequently found in autoimmune diseases, especially Sjogren syndrome and SLE.[13] In the latter, various degrees of defects and severity have been reported.[6] Impairment of distal acidification mechanisms can develop when there is a true failure to secrete H+ (secretory defect) or when there is secondary impairment due to increased back-leak of secreted H+ (gradient defect) or an inability to generate or maintain a distal lumen-negative transepithelial difference (voltage-dependent defect).[14] In this case, the patient fulfilled nearly all of the criteria for DRTA as she presented hyperchloremic metabolic acidosis with normal anion gap, hypokalemia and elevated urine anion gap, except for the urine pH criteria. However, as Richardson and Halperin[15] demonstrated, the urine pH is not a reliable subrogate of acid excretion as contrary to the urinary anion gap, because in the context of acute metabolic acidosis, there is a lag period required to induce the full renal ammoniagenic capacity; therefore, this explains the absence of elevated pH in this particular case and the utility of urinary anion gap.
In patients with SLE, all these pathogenic mechanisms of DRTA have been identified.[6] A secretory defect seems to be more frequent. In this case, hypokalemia is most frequently associated, and other complications like nephrocalcinosis and hypocitraturia can be present.[14] However, reports of preserved intercalated cell H+-ATPase by histological confirmation presumably associated with a voltage-dependent defect and development of hyperkalemic variety of dRTA is another important consideration.[6],[16] Hyporeninemic hypoaldosteronism with type 4 RTA has been also found in SLE, although the pathogenic mechanism has not been confirmed in all cases.[6],[17]
In conclusion, we describe two rare entities (NDI and DRTA) presenting as SLE renal activity, confirmed by the DDAVP test and biochemical criteria. The incidence of both diseases is low, and reported cases related to SLE are anecdotical. Regarding NDI, it is crucial to have a low threshold of suspicion when hypernatremia and an inappropriate urinary concentration response are present. In these cases, performing a confirmation test, whether it is a DDAVP or a water deprivation test, can lead to an opportune treatment and better outcomes.
Conflict of interest: None declared.
References 
Correspondence Address:
Guillermo Flores
Department of Internal Medicine, Hospital de Especialidades de Centro Médico Nacional “Siglo XXI”, Instituto Mexicano del Seguro Social, México City, México.
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/1319-2442.367813
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