Outcome of glomerulonephritis in live-donor renal transplant recipients: A single-centre experience

Peer review under responsibility of Arab Association of Urology.

Figures & data

Table 1 The demographic characteristics of the 2000 renal transplants.

Characteristic	No GN	PTGN	P
Number of patients	1897	103
Mean (SD) recipient age, years	29.84 (10.62)	27.56 (10.55)	0.034
N (%):
Recipients age range, years
<20	363 (19.1)	30 (29.1)	0.042
20–30	595 (31.4)	31 (30.1)
30–40	572 (30.2)	28 (27.2)
40–50	295 (15.6)	11 (10.7)
>50	72 (3.8)	3 (2.9)
Sex
Male	1413 (74.5)	78 (75.7)	0.778
Female	484 (25.5)	25 (24.3)
Pre-transplant hypertension
No	799 (42.1)	42 (40.7)	0.788
Yes	1098 (57.9)	61 (59.3)
Type of blood transfusion
Donor specific	11 (0.6)	1 (0.97)	0.273
Third party	852 (44.9)	54 (52.4)
No transfusion	1034 (54.5)	48 (46.6)
Type of dialysis
Pre-emptive	79 (4.2)	1 (0.9)	0.280
Haemodialysis	1797 (94.7)	102 (99.1)
Peritoneal dialysis	21 (1.1)	–
Mean (SD) donors age, years	35.47 (10.1)	36 (10.7)	0.605
N (%)
Donors age range, years
<30	745 (39.3)	37 (35.9)	0.789
30–40	604 (31.8)	33 (32)
40–50	379 (20)	20 (19.4)
>50	169 (8.9)	13 (12.6)
Donors sex
Male	903 (47.6)	50 (48.5)	0.881
Female	994 (52.4)	53 (51.5)
Consanguinity
Parent	542 (28.6)	35 (34)	0.238
Sibling	890 (46.9)	46 (44.7)	0.655
Off-spring	29 (1.5)	1 (0.97)	0.650
Emotionally related	116 (6.1)	6 (5.8)	0.905
Other relative	101 (5.3)	4 (3.9)	0.523
Unrelated	219 (11.5)	11 (10.7)	0.789
Blood groups, recipient/donor
Same	1527 (80.5)	80 (77.7)	0.482
Different (but compatible)	370 (19.5)	23 (22.3)
HLA Class I mismatch
Zero	148 (7.8)	6 (5.8)	0.181
One	215 (11.3)	16 (15.5)
Two	952 (50)	58 (56.3)
Three	294 (15.5)	16 (15.5)
Four	129 (6.8)	4 (3.9)
Undetermined	159 (8.4)	3 (2.9)
HLA Class II (DR) mismatch
Zero	195 (10.3)	10 (9.7)	0.452
One	1656 (87.3)	93 (90.3)
Two	2 (0.1)	–
Undetermined	44 (2.3)	–
Transplant received
First	1821 (96)	101 (98.1)	0.562
Second	73 (3.8)	2 (1.9)
Third	3 (0.2)	–
Ischaemia time, min
<30	217 (11.4)	9 (8.7)	0.672
30–60	1378 (72.6)	76 (73.8)
>60	302 (15.9)	18 (17.5)
Time to diuresis
Immediate	1745 (92)	94 (91.3)	0.792
Delayed	152 (8)	9 (8.7)
Number of renal arteries
One	1681 (88.6)	95 (92.2)	0.975
Two	193 (10.2)	8 (7.8)
Three	21 (1.1)	–
Four	1 (0.05)	–
Five	1 (0.05)	–

HLA, human leucocyte antigen.

Figure 1 Incidence of GN after transplantation. Post-transplantation incidence of recurrent GN (solid line) and de novo GN (dashed line) were significantly higher than transplant glomerulopathy (pointed line) (P = 0.039).

Table 2 Original kidney disease and immunosuppression of patients with PTGN.

	Recurrent GN, n (%)	De novo GN, n (%)	Transplant glomerulopathy, n (%)	P
Number of patients	18	15	70
Patients with pre-transplant GN
Mesangial	1 (5.6)	–	–	<0.001
Membranous nephropathy	1 (5.6)	–	1 (1.4)
FSGS	8 (44.4)	1 (6.7)	5 (7.1)
Membrano-proliferative	4 (22.2)	2 (13.3)	2 (2.8)
Crescentic GN	1 (5.6)	1 (6.7)	–
Hereditary nephritis	–	2 (13.3)	2 (2.8)
Amyloidosis	2 (11.1)	–	2 (2.8)
SLE^∗	1 (5.6)	1 (6.7)	8 (11.4)
Patients with no pre-transplant GN
Polycystic kidney	–	1 (6.7)	1 (1.4)	<0.001
Hypoplasia	–	–	2 (2.8)
Chronic pyelonephritis	–	1 (6.7)	6 (8.6)
Nephrosclerosis	–	–	2 (2.8)
ESRD	–	3 (20)	27 (38.6)
Congenital	–	–	1 (1.4)
Obstructive uropathy	–	–	1 (1.4)
Inapplicable	–	3 (20)	10 (14.3)
Induction therapy
Polyclonal antibodies	2 (11.1)	3 (20)	8 (11.4)	0.881
Monoclonal antibodies	5 (27.8)	4 (26.7)	15 (21.5)
No induction	11 (61.1)	8 (53.3)	47 (67.1)
Primary immunosuppression
Conventional based	2 (11.1)	2 (13.3)	22 (31.4)	0.197
Triple based	14 (77.7)	9 (60)	38 (54.4)
Tacrolimus based	1 (5.6)	–	–
Sirolimus based	1 (5.6)	3 (20)	8 (11.4)
Steroid avoidance	–	1 (6.7)	1 (1.4)
Alemtuzumab	–	–	1 (11.4)

∗ Systemic lupus erythematosus.

Table 3 Medical complications after transplantation in patients with PTGN.

	Recurrent GN, n (%)	De novo GN, n (%)	Transplant glomerulopathy, n (%)	P
Number of patients	18	15	70
Acute tubular necrosis
No	16 (88.9)	15 (100)	67 (95.7)	0.310
Yes	2 (11.1)	–	3 (4.3)
Hypertension
No	6 (33.3)	2 (13.3)	18 (25.7)	0.415
Yes	12 (66.7)	13 (86.7)	52 (74.3)
Post-transplantation DM
No	16 (88.9)	9 (60)	56 (80)	0.116
Yes	2 (11.1)	6 (40)	14 (20)
Medical infection
No	14 (77.8)	13 (86.7)	47 (67.1)	0.258
Yes	4 (22.2)	2 (13.3)	23 (32.9)
Hepatic impairment
No	17 (94.4)	13 (86.7)	64 (91.4)	0.730
Yes	1 (5.6)	2 (13.3)	6 (8.6)
Acute rejection
No	12 (66.7)	7 (46.7)	36 (51.4)	0.566
Acute cellular	6 (33.3)	8 (53.3)	31 (44.3)
Acute vascular	–	–	3 (4.3)
Chronic rejection
No	16 (88.9)	14 (93.3)	36 (51.4)	<0.001
Yes	2 (11.1)	1 (6.7)	34 (48.6)
Malignancy
No	17 (94.4)	13 (86.7)	68 (97.1)	0.228
Yes	1 (5.6)	2 (13.3)	2 (2.9)

Figure 2 Graft survival of the recipients who did not develop PTGN vs recipients who developed PTGN. (A) Graft survival in the recipients who developed PTGN (dashed line) was comparable to those with no PTGN (solid line) in the first 2 years. Thereafter, there was a significant drop in graft survival in the group of recipients who had PTGN vs those who did not develop PTGN (P < 0.001). (B) Graft survival in the recipients who developed de novo GN (dashed line) and transplant glomerulopathy (pointed line) was comparable to those who did not develop PTGN (solid bold line) in the first 2 years (P = 0.067). While there was a significant drop in graft survival in recipients with recurrent GN (solid thin line) vs other groups in the first 2 years. Thereafter, there was a significant drop in graft survival in the group of recipients who had PTGN (whatever the type) vs those who did not develop PTGN (P = 0.001).

Figure 3 Patient survival of the recipients who did not develop GN vs recipients who developed PTGN. (A) Patient survival in the recipients who developed PTGN (dashed line) was comparable to those with no PTGN (solid line) in the first 5 years. Thereafter, there was a significant drop in patient survival in the group of recipients who had PTGN vs those who did not develop PTGN (P = 0.048). (B) patient survival in the recipients who developed PTGN (whatever the cause) was comparable to those who did not develop PTGN in the first 5 years. Thereafter, there was a significant drop in patient survival in the group of recipients who had de novo GN (dashed line) and transplant glomerulopathy (solid line) vs those who did not develop PTGN (P = 0.005).

Table 4 Multivariate analysis of the risk factors for developing PTGN.

	Regression estimate (B)	Relative risk (95% CI), Exp B	P
Recipient age, years
<20	–	1
20–30	–0.929	0.40 (0.152–1.03)	0.057
31–40	–0.512	0.60 (0.26–1.39)	0.231
41–50	–0.330	0.72 (0.25–2.1)	0.540
>50	0.793	0.45 (0.039–5.23)	0.525
Original kidney disease
No GN	–	1
GN	0.015	1.01 (0.566–1.821)	0.959
Donor age, years
<30	–	1
31–40	0.570	1.76 (1.04–3)	0.035
41–50	0.602	1.82 (0.977–3.41)	0.059
>50	0.289	1.33 (0.657–2.71)	0.424
Recipient sex match
Male–male	–	1
Male–female	–0.228	0.796 (0.319–1.98)	0.625
Female–male	0.397	1.48 (0.743–2.97)	0.263
Female–female	0.451	1.57 (0.576–4.27)	0.378
Consanguinity
Parent	–	1
Sibling	0.518	1.67 (0.47–5.97)	0.424
Off-spring	1.261	3.52 (0.1–125)	0.489
Other relative	0.898	2.45 (0.57–10.6)	0.231
Unrelated	1.220	3.38 (0.82–14.1)	0.093
Donor/recipient blood group match
Same	–	1
Different	–0.869	0.42 (0.23–0.77)	0.005
Blood transfusion
No	–	1
Yes	–0.451	0.64 (0.39–1.05)	0.075
Ischaemia time, min
<30	–	1
30–60	–0.711	0.491 (0.194–1.27)	0.134
>60	–0.437	0.65 (0.196–2.13)	0.473
Time to diuresis
Immediate	–	1
Delayed	0.473	1.60 (0.58–4.47)	0.366
Induction therapy
No	–	1
Polyclonal	0.217	1.24 (0.361–4.28)	0.731
Monoclonal	–0.271	0.763 (0.262–2.22)	0.619
Maintenance immunosuppression
Conventional	–	1
CsA based	0.278	1.32 (0.74–2.34)	0.343
Tacrolimus	1.855	6.39 (0.76–54)	0.089
Sirolimus	1.536	4.64 (2.14–10)	<0.001
Steroid avoidance	0.589	1.80 (0.386–8.4)	0.454
Steroids in first 3 months, g
<5	–	1
5–10	−0.088	0.92 (0.45–1.89)	0.812
>10	0.631	1.87 (0.78–4.5)	0.158

CsA, cyclosporin A.

Table 5 Multivariate analysis of the risk factors of graft survival.

	Regression estimate (B)	Relative risk (95% CI), Exp B	P
Recipient age, years
<20	–	1
20–30	0.070	1.07 (0.80–1.44)	0.640
31–40	0.262	1.30 (0.93–1.81)	0.120
41–50	0.601	1.82 (1.24–2.67)	0.002
>50	0.562	1.75 (0.95–3.22)	0.070
Original kidney disease
No GN	–	1
GN	–0.071	0.93 (0.68–1.27)	0.652
Donor age, years
<30	–	1
31–40	–0.257	0.77 (0.61–0.99)	0.038
41–50	0.245	1.27 (0.94–1.74)	0.118
>50	0.109	1.12 (0.73–1.71)	0.615
Recipient sex match
Male–male	–	1
Male–female	0.127	1.14 (0.82–1.56)	0.439
Female– male	0.018	1.02 (0.67–1.54)	0.931
Female–female	0.059	1.06 (0.78–1.44)	0.705
Consanguinity
Parent	–	1
Sibling	–0.036	0.97 (0.65–1.43)	0.858
Off-spring	–0.303	0.74 (0.56–0.97)	0.028
Other relative	0.771	2.16 (0.95–4.92)	0.066
Unrelated	0.249	1.28 (0.83–1.99)	0.266
Donor/recipient blood group match
Same	–	1
Different	–0.294	0.75 (0.59–0.95)	0.016
Blood transfusion
No	–	1
Donor specific	–0.027	0.97 (0.79–1.2)	0.800
Third party	–0.077	0.93 (0.36–2.4)	0.873
Ischaemia time, min
<30	–	1
30–60	0.205	1.23 (0.97–1.5)	0.089
>60	0.327	1.39 (0.94–2.05)	0.103
Time to diuresis
Immediate	–	1
Delayed	0.140	1.15 (0.83–1.6)	0.395
Induction therapy
No	–	1
Polyclonal	0.688	1.99 (1.53–2.6)	<0.001
Monoclonal	–0.448	0.64 (0.35–1.18)	0.151
Maintenance immunosuppression
Conventional	–	1
CsA based	0.116	1.12 (0.27–4.6)	0.872
Tacrolimus	–0.142	0.87 (0.21–3.5)	0.843
Steroids in first 3 months, g
<5	–	1
5–10	–0.149	0.86 (0.68–1.1)	0.216
>10	–0.044	0.96 (0.69–1.3)	0.786
Rejection
No	–	1
One acute rejection	0.301	1.35 (1–1.8)	0.049
⩾two acute rejections	0.681	1.97 (1.45–2.7)	<0.001
Chronic rejection	0.878	2.41 (1.9–3)	<0.001
PTGN
No	–	1
Recurrent GN	–0.226	0.79 (0.56–1.13)	0.207
de novo GN	1.205	3.33 (1.5–7.4)	0.003
Transplant GN	0.530	1.69 (0.77–3.76)	0.191

Table

Treatment	Clinically relevant^∗ recurrent risk^†, %	Risk of graft loss due to recurrence 5–10 years after transplantation^†, %	Prevention/treatment strategies
IgAN	13–46	2–16	ACEI and/or ARB for patients with proteinuria ± renal impairment due to recurrent IgAN [22,23]
FSGS	20–50	13–20	Avoid living donors for patients with history of rapid graft loss from recurrence [24]
			Pre-emptive perioperative plasmapheresis (PP) for 2 weeks for patients with high risk of recurrence [25,26]
			Chronic PP with or without cyclophosphamide or cyclosporine for patients with relapse after initial course of PP [27–29]
			Avoid omission of calcineurin inhibitors in sirolimus-based immunosuppressive regimen [30,31]
			Avoid induction therapy [32,33]
MPGN
Type I	20–25	≈15	No effective preventive or treatment measures
Type II	80–100	15–30	Exclude secondary causes
Membranous nephropathy	10–30	10–15	No effective preventive or treatment measures
			Exclude secondary causes
ANCA-associated glomerulonephritis	≈17	6–8	Defer transplant till disease inactive [34]
			Cyclophosamide for recurrence [34,35]
			Combine therapy with PP, cyclophosphamide ± i.v. immunoglobulin for recurrence with high titre of ANCA and cellular crescents in renal biopsies [35,37]
SLE	2–9	2–4	Defer transplant until disease inactive [38,39]
			Consider mycophenolate mofetil for recurrence [40,41]
Anti-GBM	Rare	Rare	Defer transplant until disease inactive
			Combine therapy with PP/immunoabsorption and cyclophosphamide for recurrence with high anti-GBM titre and cellular crescents in renal biopsies [36,42]

∗ Clinically relevant refers to patients with clinical symptoms of proteinuria/haematuria/renal impairment.

† % of transplanted patients. IgAN, recurrent IgA nephropathy; SLE, systemic lupus erythematosus; ACEI, angiotensin-converting enzyme inhibitor; ANCA, anti-neutrophil cytoplasmic autoantibody; GBM, glomerular basement membrane.