Deposit of Ca-P or Ca-oxalate in the kidney parenchyma(多在medulla(因為是沉積在thin limbs, IMCD)見下述pathogenesis); <3% involve cortex; involve cortex者多有其他severe cortical diseases(like previous renal cortical necrosis in pregnancy or cGN)或是oxalosis(cortex+medulla) or renal allograft rejection(見-Renal echo:summary of renal parenchymal disease and D/D list)
Caused by increased urine (Ca, P or oxalate)(不一定要hypercalcemia), 基本上也會有nephrolithiasis, 但不一定會有(機制不明), 反過來有nephrolithiasis者常常沒有nephrocalcinosis(回思臨床上那麼多人有renal stones, 但的確很少看到有人合併nephrocalcinosis...)
一開始在inner medullary (papillary) interstitium in the BM of the thin limbs of the loop of Henle, and IMCD形成Ca-P crystals, 接著可破入tubular lumen成為Ca-oxalate crystal的nidus or 進入interstitium
CYP24A1突變(NEJM 2011; PMID 21675912)：25-hydroxyvitamin D 24-hydroxylase功能喪失導致1,25(OH)2D降解障礙，引起高血鈣、高尿鈣與特發性嬰兒高血鈣/腎鈣質沉著症〔PMID 21675912〕
Milk alkali syndrome
Primary hyperparathyroidism
20% nephrocalcinosis
Congenital diseases
Congenital hypothyroidism
因為一般intact mitochondria可堆積Ca against concentration gradient in proximal or distal renal tubular cells; 但Congenital hypothyroidism沒辦法, 導致intracellular hypercalcemia-->nephrocalcinosis
Williams-Beuren syndrome
機轉不是很明確, 但這些病人會higher SCa(雖然大多WNL)而導致hypercalciuria and infrequently results in nephrocalcinosis
有些studies發現和1, 25 OH vitamin D↑, ↑vitamin D sensitivity and defective calcitonin synthesis/release有關
Ca normal + hypercalciuria
RTA type I
因為metabolic acidosis-->1. bone放出Ca, P由kidney排出(抑制renal再吸收Ca and Mg(by ↓TRPV5 and ↓TRPM6)), 2.hypocitraturia(metabolic acidosis本身會使p. tubules再吸收Citrate↑); 此外urine alkalization-->nephrocalcinosis(60-80%)
Nephrocalcinosis tends to be uniform and distributed throughout the renal pyramids bilaterally
Chronic hypokalemia
回思增加K intake-->↓Ca excretion(見Nephrology-CKD-Urinalysis and renal stones-12.Crystalluria-Renal stones(T-H protein生理上可↓crystal formation)-Chronic Tx-if Ca stone-diet)
Loop diuretics(高劑量, 長時間), Bartter syndrome
Bartter症候群(TAL鹽分重吸收缺陷)伴高尿鈣與常併發髓質腎鈣化〔PMID 33509356〕；KDIGO共識指引(Kidney Int 2017; PMID 28003083)強調Gitelman症候群(SLC12A3突變)特徵為低尿鈣且無腎鈣化，以此鑑別〔PMID 28003083〕
Medullary sponge kidney
Nonhereditary developmental disorder with ectasia and cystic dilation of the distal collecting ducts, 多bilateral, normal size kidney with medullary nephrocalcinosis, 可renal stones, 可type I/IV RTA
Brenner(p1110):Small calculi form in the distal collecting tubules, probably because of stasis; The calcifications are small, round, and within the peak of the pyramid adjacent to the calyx, 所以也可以變成renal stone; 此擴張/stasis處也容易infection