Childhood nephrolithiasis and nephrocalcinosis caused by metabolic diseases and renal tubulopathy: A retrospective study from 2 tertiary centers

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Figure 1
- A flow diagram showing how patients were assigned to the different groups. FHHNC: familial hypomagnesemia with hypercalciuria and nephrocalcinosis, dRTA: distal renal tubular acidosis

Table 1

- Patients’ characteristics according to disease group.

Characteristics	Metabolic	FHHNC	dRTA
Characteristics	n (%)
Age (months), mean±SD	73.5±54.4	70.2±43.9	72.6±52.2
Gender
Male	32 (60.4)	6 (33.3)	9 (60.0)
Female	20 (39.6)	12 (66.7)	6 (40)
Creatinine (µmol), mean±SD	103.7±184.9	71.8±48.2	72.7±93.5
Consanguinity*	40 (75.5)	17 (100)	9 (60.0)
Family history of renal disease	18 (34.0)	15 (88.2)	4 (26.7)

FHHNC: familial hypomagnesemia with hypercalciuria and nephrocalcinosis, dRTA: distal renal tubular acidosis, SD: standard deviation, *35 children of the metabolic group had parents who are first degree cousins, while 5 children with second degree cousins, FHHNC group: 15 children with first degree cousins and 2 with second degree cousins, dRTA group: 8 children with first degree cousins and one with second degree cousin

Table 2

- Patients’ characteristics according to metabolic group.

Characteristics	Metabolic
	Hypercalciuria	Hyperoxaluria	Cystinuria	Hyperuricosuria
	n (%)
Age (months), mean±SD	59.2±57.9	70.6±45.4	91.0±58.3	56.3±75.9
Gender
Male	9 (69.2)	12 (60.0)	9 (52.9)	2 (66.7)
Female	4 (30.8)	8 (40.0)	8 (47.1)	1 (32.3)
Creatinine (µmol), mean±SD	37.2±17.5	178.3±262.6	77.5±130.5	44±26.9
Consanguinity	8 (61.5)	16 (80.0)	14 (82.4)	2 (66.7)
Family history of renal disease	4 (30.8)	8 (40.0)	6 (35.3)	0 (0.0)

Table 3

- Laboratory and radiological findings according to metabolic group.

Characteristics	Hypercalciuria	Hyperoxaluria	Cystinuria	Hyperuricosuria	P-value
Characteristics	mean±SD
Laboratory urine results (mmol/mmol)
Calcium/creatinine	1.59±0.68	1.12±1.57	2.06±6.87	0.84±0.79	0.899
Oxalate/creatinine	0.24±0.02	26.51±67.09	0.03±0.02	0.04±0.03	0.186
Cysteine/creatinine	5.73±4.68	6.21±6.19	132.03±70.60	46.32±63.80	<0.001
Citrate/creatinine	2.92±2.33	7.57±13.83	5.49±6.73	12.19±8.29	0.36
Uric acid/creatinine	0.34±0.19	0.35±0.19	0.40±0.23	2.12±1.34	<0.001
Radiology findings, n (%)
Stones	11 (84.6)	16 (80)	17 (100)	3 (100)	0.211
Nephrocalcinosis	2 (15.4)	4 (20)	0 (0.0)	0 (0.0)
Stone number, n (%)
Single stone	4 (36.4)	4 (25)	4 (23.5)	1 (33.3)	0.860
Multiple stones	7 (63.6)	12 (75)	13 (76.5)	2 (66.7)
Stone locations, n (%)
Kidney	19 (90.9)	12 (75)	6 (35.3)	3 (100)	0.006
Bladder	0 (0.0)	2 (12.5)	16 (94.1)	0 (0.0)	<0.001
Ureteric	2 (18.2)	7 (43.8)	5 (29.4)	0 (0.0)	0.399

Table 4

- Details of genetic analysis.

FHHNC: familial hypomagnesemia with hypercalciuria and nephrocalcinosis, dRTA: distal renal tubular acidosis, AGXT: alanine-glyoxylate and serine-pyruvate aminotransferase, CLDN16: Claudin-16, SLC3A1: solute carrier family 3 member 1, AGXT was homozygous in 9 children and 2 combined heterozygous in 2 children while all mutations of SLC3A1 were homozygous as well as CLDN16 were homozygous in 7 children

Table 5

- Clinical presentation and chemistry results among patients with FHHNC and dRTA.

Urine results	FHHNC	dRTA	Normal range
Urine results	Mean (95% CI)
Calcium/creatinine (mmol/mmol)	2.43 (1.62-3.24)	1.51 (0.74-2.28)	1-3 years: >1.5
			4-7 years: >1
			8-14 years:>0.7
FEMg% (mean)	15.46 (11.09-19.82)	2.52 (1.24-3.79)	<5%
TRP% (mean)	90.66 (86.48-94.84)	83.66 (76.92-90.41)	78-91%
Serum results (mmol/L)
Serum sodium	139.3 (138.50-140.27)	140.6 (138.60-142.72)	136-145
Serum potassium	3.87 (3.61-4.13)	3.14 (2.90-3.38)	3.5-5.1
Serum chloride	100.94 (98.88-103.00)	109.53 (105.51-113.54)	98-107
pH	7.48 (7.46-7.50)	7.25 (7.21-7.30)	7.35-7.45
Serum HCO₃ (mmol)	29.83 (29.31-30.35)	17.80 (16.21-19.38)	22-26
Serum calcium	2.24 (2.15-2.33)	2.28 (2.22-2.33)	2.12-2.52
Serum phosphate	1.38 (1.21-1.56)	1.25 (0.96-1.53)	0.81-1.58
Serum magnesium	0.54 (0.50-0.59)	0.81 (0.76-0.86)	0.70-1.0

FHHNC: familial hypomagnesemia with hypercalciuria and nephrocalcinosis, dRTA: distal renal tubular acidosis, FTT: failure to thrive, UTI: urinary tract infection, FEMg%: fraction excretion of magnesium, TRP%: transtubular reabsorption of phosphate, pH: potential of hydrogen, HCO₃: bicarbonate

Item	Range (month)	Range (year)	Cut-off level
Ca/creatine (mmol/mmol)	0-12	0-1	2.2
	12-36	1-3	1.5
	36-60	3-5	1.1
	60-84	5-7	0.8
	>84	>7	0.6
Oxalate/creatine (mmol/mmol)	0-12	0-1	0.17
	12-24	1-2	0.13
	24-36	2-3	0.1
	36-60	3-5	0.08
	60-84	5-7	0.07
	>84	>7	0.06
Cystine/creatine (mmol/mol)	0-1	0≥1	85
	1-6		53
	>6		18
Citrate/creatine (mmol/mmol)	0-60	0-5	0.12
Citrate/creatine (mmol/mmol)	>60	>5	0.08
Uric acid/creatine (mmol/mmol)	0-12	0-1	1.5
	12-36	1-3	1.3
	36-60	3-5	1
	60-120	5-10	0.6
	>120	>10	0.4