The medical records, premortem biopsy specimens, and autopsy materials from 36 patients with acquired immune deficiency syndrome (AIDS) were reviewed. The majority of the patients were homosexual men. Widely metastatic Kaposi's sarcoma was seen in eight patients, while tumor was confined to the skin in an additional ten. Four patients had high-grade lymphomas. Thirty-five of the 36 patients had at least one opportunistic infection at some point in the course of their illness. Many patients had multiple infectious agents. The most consistent and striking autopsy finding was a severe depletion of lymphoid tissues. Death in the majority (83%) of the patients was attributable to opportunistic infections affecting most commonly the respiratory tract (64%) and meninges (11%). Three patients (9%) died with widely metastatic Kaposi's sarcoma and secondary hemorrhage. ( JAMA 1984;252:1152-1159)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=jama&articleId=394154&pdfFileName=jama_252_9_018.pdf

Autopsy findings in the acquired immune deficiency syndrome.

We have used homologous recombination to disrupt the mouse gene coding for the NaK2Cl cotransporter (NKCC2) expressed in kidney epithelial cells of the thick ascending limb and macula densa. This gene is one of several that when mutated causes Bartter's syndrome in humans, a syndrome characterized by severe polyuria and electrolyte imbalance. Homozygous NKCC2-/- pups were born in expected numbers and appeared normal. However, by day 1 they showed signs of extracellular volume depletion (hematocrit 51%; wild type 37%). They subsequently failed to thrive. By day 7, they were small and markedly dehydrated and exhibited renal insufficiency, high plasma potassium, metabolic acidosis, hydronephrosis of varying severity, and high plasma renin concentrations. None survived to weaning. Treatment of -/- pups with indomethacin from day 1 prevented growth retardation and 10% treated for 3 weeks survived, although as adults they exhibited severe polyuria (10 ml/day), extreme hydronephrosis, low plasma potassium, high blood pH, hypercalciuria, and proteinuria. Wild-type mice treated with furosemide, an inhibitor of NaK2Cl cotransporters, have a phenotype similar to the indomethacin-rescued -/- adults except that hydronephrosis was mild. The polyuria, hypercalciuria, and proteinuria of the -/- adults and furosemide-treated wild-type mice were unresponsive to inhibitors of the renin angiotensin system, vasopressin, and further indomethacin. Thus absence of NKCC2 in the mouse causes polyuria that is not compensated elsewhere in the nephron. The NKCC2 mutant animals should be valuable for uncovering new pathophysiologic and therapeutic aspects of genetic disturbances in water and electrolyte recovery by the kidney.

https://www.pnas.org/content/pnas/97/10/5434.full.pdf

Uncompensated polyuria in a mouse model of Bartter's syndrome

Evidence for a prostaglandin-independent defect in chloride reabsorption in the loop of henle as a proximal cause of Bartter's syndrome

Inherited renal tubular disorders associated with hypokalemic alkalosis (Bartter-like syndromes) can be subdivided into at least three clinical phenotypes: (i) the hypocalciuric-hypomagnesemic Gitelman variant; (ii) the classic variant; and (iii) the antenatal hypercalciuric variant (also termed hyperprostaglandin E syndrome). Mutations in the Na-Cl cotransporter (NCCT) underlie the pathogenesis of the Gitelman variant and mutations in the Na-K-2Cl cotransporter (NKCC2) have recently been identified in the antenatal hypercalciuric variant. We now describe mutations in the gene encoding the inwardly-rectifying potassium channel, ROMK, in eight kindreds with the antenatal variant of Bartter syndrome. These findings indicate that antenatal Bartter syndrome is genetically heterogeneous and provide new insights into the molecular pathogenesis of Bartter-like syndromes.

/pdf/mutations-in-the-gene-encoding-the-inwardly-rectifying-renal-2iro2xrbjm.pdf

Mutations in the Gene Encoding the Inwardly-Rectifying Renal Potassium Channel, ROMK, Cause the Antenatal Variant of Bartter Syndrome: Evidence for Genetic Heterogeneity

Bartter's Syndrome

The pathogenesis of Bartter's syndrome. Functional and histologic studies.

https://www.amjmed.com/article/0002-9343(82)90928-7/pdf

Independent roles of prostaglandins and the renin-angiotensin system in abnormal vascular reactivity in Bartter's syndrome

A Case of Primary Macroglobulinemia with Lung Involvement

A 50-year-old man with sporadic renal medullary cystic disease associated with moderate renal failure, severe anemia, dehydration and osteodystrophy, and without edema, hypertension or remarkable urine sediment was studied. Hyperchloremic acidosis and hypokalemia were found in this patient, which could be explained as a consequence of proximal renal tubular acidosis, since, during the normalization of plasma bicarbonate level by the adminstration of sodium bicarbonate, urinary potassium excretion was increased and urinary pH was further increased to 8.1. In addition, he had generalized aminoaciduria and increased clearance of phosphate and uric acid. Particularly the lysozyme clearance (Cly/Ccr) in this patient was significantly higher than in patients with chronic glomerunephritis, and equal to the value of Fanconi's syndrome. The presence of salt-wasting, hyperchloremic metabolic adidosis, aminoaciduria, hyperuricosuria and "tubular proteinuria" suggests that the patient with medullary cystic disease is associated with multiple proximal tubular dysfunction. The finding of renal biopsy is presented which suggests that this disorder represents a toxic nephropathy.

https://www.jstage.jst.go.jp/article/internalmedicine1962/17/4/17_4_328/_pdf

Toshio Fukui

Papers

The pathogenesis of Bartter's syndrome. Functional and histologic studies.

Independent roles of prostaglandins and the renin-angiotensin system in abnormal vascular reactivity in Bartter's syndrome

A Case of Primary Macroglobulinemia with Lung Involvement

A Case of Renal Medullary Cystic Disease with Proximal Tubular Dysfunction

[A case of polyarteritis nodosa with lung involvement (author's transl)].