kdigo gn guideline update – evidence summary …...1 kdigo gn guideline update – evidence...

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KDIGO GN Guideline update – Evidence summary

Idiopathic focal segmental glomerulosclerosis (FSGS) in adults

Immunosuppressive therapy FSGS PICO question In patients with biopsy-proven FSGS in adults what immunosuppressive agents compared to no treatment/placebo or other immunosuppressive therapy improves efficacy outcomes (all-cause mortality, end-stage kidney disease, ≥50% loss of GFR, annual loss of GFR, complete remission) and reduces adverse effects (infection, and malignancy)? Search strategy and selection Keywords for idiopathic focal segmental glomerulosclerosis (FSGS), and immunosuppressive therapy were used to search the Cochrane Kidney and Transplant Specialized Registry of studies for all randomised controlled trials (RCTs) published up to May 2018. Studies contained in the register are identified through search strategies for CENTRAL, MEDLINE, and EMBASE. Search results The 2018 Cochrane review search update identified 45 relevant reports from the Cochrane Kidney and Transplant Specialized Registry of studies. Twelve of these reports were excluded because they were not RCTs, were the wrong population or because were the wrong intervention. There were four primary studies (33 reports) and three reports of a previously included study identified. Combined with the 2008 Cochrane review, there was 11 studies (51 reports) included with 360 participants. Eleven comparisons were identified:

1. Cyclosporin versus mycophenolate mofetil plus dexamethasone (1 study, 138 participants) 2. Cyclosporin plus low dose prednisone versus prednisone alone (1 study, 49 participants) 3. Cyclosporin plus prednisolone versus methylprednisolone (1 study, 23 participants) 4. Cyclosporin plus prednisone versus chlorambucil plus prednisone ( 1 study, 57 participants) 5. Prednisolone plus chlorambucil versus no treatment (1 study, 15 participants) 6. Cyclosporin versus supportive therapy (1 study, 19 participants) 7. Mycophenolate mofetil versus prednisone (1 study, 33 participants) 8. Dexamethasone 2 weekly versus dexamethasone 4 weekly (1 study, 8 participants) 9. Fresolimumab versus placebo (1 study, 36 participants) 10. Adalimumab versus rosiglitazone (1 study, 21 participants)* 11. Adalimumab versus galactose or conservative therapy (1 study, 21 participants)

* Data from the FONT I 2009 study could not be meta-analysed as different outcomes were reported for the different treatment arms.

FONT I 2009 Study - Joy MS, et al. Phase I trial of rosiglitazone in FSGS: I. Report of the FONT Study Group. Clinical Journal of the American Society of Nephrology: CJASN 2009;4(1):39-47.

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Summary of the main findings Immunosuppressive therapy versus no treatment

• We are uncertain whether prednisolone plus chlorambucil compared with no treatment ( 1 study, 15 participants) increases or decreases complete remission or doubling of serum creatinine due to study limitations and very serious imprecision in the effect estimate. Other critical and important outcomes were not reported in the RCT.

• Cyclosporin compared to no treatment may have little or no effect on doubling of serum creatinine (RR 0.60, 95%CI 0.25 to 1.46), based on data from 19 patients in one RCT. The effects on other critical and important outcomes are uncertain because of very low certainty of the evidence or they were not reported in the RCT.

Cyclosporin compared with other immunosuppressive therapy

• Cyclosporin compared with MMF plus dexamethasone (1 study, 138 participants) may have little or no effect on the following: all-cause mortality (RR 0.18, 95%CI 0.01 to 3.75), end stage kidney disease (RR 2.29, 95%CI 0.46 to 11.41), ≥ 50% GFR loss (RR 4.58, 95%CI 0.55 to 11.41), infection (RR 1.09, 95%CI 0.61 to 1.93), infection requiring hospitalization (RR 0.65, 95%CI 0.22 to 1.96), total hospitalization (RR 0.79, 95%CI 0.39 to 1.57), and complete remission (RR 2.41, 95%CI 0.87 to 6.71).

• Cyclosporin plus low dose prednisone compared with prednisone alone (1 study, 49 participants) may decrease end stage kidney disease (RR 0.35, 95%CI 0.12 to 0.98) and may increase partial remission (RR 7.96, 95%CI 1.09 to 58.15). There was too few who experienced complete remission to determine an effect. Compared with prednisone alone, cyclosporin plus low dose prednisone may have little or no effect on doubling of serum creatinine (RR 1.18, 95%CI 0.72 to 1.94), and other critical and important outcomes were not reported in the RCT.

• It is uncertain if complete remission is increased by cyclosporin plus prednisolone compared with treatment methylprednisolone, due to very serious imprecision (wide confidence intervals that cross the null with appreciable benefit and harm) and serious risk of bias. Other critical and important outcomes were not reported in the RCT (1 study, 25 participants).

• Cyclosporin plus prednisone compared with chlorambucil plus prednisone was examined in one small RCT (58 participants). It is uncertain if this increases or decreases complete remission or end-stage kidney disease, due to very serious risk of bias and very serious imprecision. Other critical and important outcomes were not reported in the RCT.

Mycophenolate mofetil versus prednisone

• Mycophenolate mofetil compared with prednisone may have little or no effect on complete remission (RR 1.05, 95%CI 0.58 to1.88), based on data from 33 patients in one RCT. The effects on infection or GFR (ml/min) are uncertain, due to serious risk of bias and very serious imprecision. Other critical and important outcomes were not reported in the RCT.

Dexamethasone 2 weekly vs. Dexamethasone 4 weekly (

• We are uncertain whether dexamethasone two-weekly compared to four-weekly increases or decreases partial remission or GFR (ml/min), due to serious risk of bias and very serious imprecision (1 study, 7 participants). Other critical and important outcomes were not reported in the RCT.

Biologic therapy

• There were too few partial remission events, to determine whether there is difference between fresolimumab (1mg and 4mg) compared to placebo. Other critical and important outcomes were not reported in the small RCT (36 participants).

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• Compared to galactose or conservative therapy, we are unable to determine the effect of adalimumab on critical and important outcomes, either because there were two few events, study limitations and very serious imprecision in the effect estimates or they were not reported in the small RCT (21 participants)

Effect modifiers The following effect modifiers were considered:

• Kidney function (GFR, proteinuria, presence of albuminuria) • Relapse or resistance disease • Gender • Etiology, in particular adaptive FSGS vs. genetic or “idiopathic”

There was insufficient data to allow for the assessment of effect modifiers.

Studies from the 2012 KDIGO GN guideline evidence tables not included in 2018 evidence review.

No studies were found in the 2012 guideline that were not included in the 2018 review.

21 Aug 2018 - KDIGO Clinical Practice Guideline for Glomerulonephritis PICO (14.1) Population: Patients with focal segmental glomerulosclerosis Intervention: Prednisolone plus chlorambucil Comparator: No treatment

Outcome Timeframe

Study results and measurements

Absolute effect estimates Certainty in effect estimates

(Quality of evidence) Plain text summary No treatment

Prednisolone plus

chlorambucil

All-cause mortality

(CI 95% - )

No studies were found that looked at all-cause

mortality Difference: fewer

End-stage kidney disease

(CI 95% - )

No studies were found

that looked at end-stage kidney disease Difference: fewer

≥50% loss of GFR

(CI 95% - )

No studies were found that looked at ≥50%

loss of GFR Difference: fewer

Malignancy

(CI 95% - )


that looked at malignancy Difference: fewer

Infection

(CI 95% - )

No studies were found that looked at infection

Difference: fewer

Complete remission

Relative risk: 1.75 (CI 95% 0.2 - 15.41)

Based on data from 15 patients in 1 studies1 Follow up 6 months

143 per 1000

250 per 1000 Very Low

Due to serious risk of bias, Due to very serious imprecision2

We are uncertain whether prednisolone

plus chlorambucil compared with no

treatment increases or decreases complete

remission

Difference: 107 more per 1000 (CI 95% 114 fewer - 2061 more)

Doubling of serum creatinine

Relative risk: 0.3 (CI 95% 0.01 - 6.29)


143 per 1000



We are uncertain whether prednisolone

plus chlorambucil compared with no

treatment increases or decreases doubling

serum creatinine

Difference: 100 fewer per 1000 (CI 95% 142 fewer - 756 more)

Annual GFR loss 3 years

Measured by: Scale: - Lower better

No studies were found that looked at annual

GFR loss Difference: null lower

1. Primary study Imbasciati 1980 Baseline/comparator: Control arm of reference used for intervention . 2. Risk of bias: Serious. Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias; Imprecision: Very

Serious. Wide confidence intervals, Only data from one study, Low number of patients; 3. Primary study Imbasciati 1980 Baseline/comparator: Control arm of reference used for intervention .

4. Risk of bias: Serious. Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias; Imprecision: Very Serious. Wide confidence intervals, Only data from one study, Low number of patients;

21 Aug 2018 - KDIGO Clinical Practice Guideline for Glomerulonephritis PICO (14.2) Population: Patients with focal segmental glomerulosclerosis Intervention: Cyclosporin Comparator: No treatment

Outcome Timeframe



(Quality of evidence) Plain text summary No treatment Cyclosporin

All-cause mortality

(CI 95% - )




Relative risk: 0.33 (CI 95% 0.02 - 7.39)

Based on data from 22 patients in 1 studies Follow up Median 18

months for cyclosporin group and 24 months for the no treatment group

91 per 1000

30 per 1000

Very Low Due to serious risk of bias, Due to

very serious imprecision1

We are uncertain whether cyclosporin compared with no

treatment increases or decreases end-stage

kidney disease Difference: 61 fewer per 1000

(CI 95% 89 fewer - 581 more)

≥50% loss of GFR

Relative risk: 0.33 (CI 95% 0.04 - 2.73)

Based on data from 22 patients in 1 studies2 Follow up Median 18


273 per 1000

90 per 1000




treatment increases or decreases ≥50% loss of

GFR Difference: 183 fewer per 1000

(CI 95% 262 fewer - 472 more)

Infection

Relative risk: 0.9 (CI 95% 0.24 - 3.38)



333 per 1000

300 per 1000




treatment increases or decreases infection


Malignancy

(CI 95% - )



Complete remission

Relative risk: 4.55 (CI 95% 0.25 - 83.7)



0 per 1000

0 per 1000



There were too few who experienced the

complete remission, to determine whether

cyclosporin compared to no treatmetn made a

difference

Difference: 0 fewer per 1000 (CI 95% 0 fewer - 0 fewer)

Doubling of serum creatinine

Relative risk: 0.6 (CI 95% 0.25 - 1.46)



667 per 1000

400 per 1000

Low Due to serious risk of bias, Due to

serious imprecision9

Cyclosporin compared to no treatment may

have little or no difference on doubling

of serum creatinine Difference: 267 fewer per 1000

(CI 95% 500 fewer - 307 more)




Difference: null lower

GFR loss


2. Primary study Ponticelli 1993a Baseline/comparator: Control arm of reference used for intervention . 3. Risk of bias: Serious. Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias; Imprecision: Very

Serious. Wide confidence intervals, Only data from one study, Low number of patients; 4. Primary study Ponticelli 1993a Baseline/comparator: Control arm of reference used for intervention . 5. Risk of bias: Serious. Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias; Imprecision: Very

Serious. Wide confidence intervals, Only data from one study, Low number of patients; 6. Primary study Ponticelli 1993a Baseline/comparator: Control arm of reference used for intervention . 7. Risk of bias: Serious. Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias; Imprecision: Very

Serious. Wide confidence intervals, Only data from one study, Low number of patients; 8. Primary study Ponticelli 1993a Baseline/comparator: Control arm of reference used for intervention . 9. Risk of bias: Serious. Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias; Imprecision:

Serious. Only data from one study, Low number of patients;

21 Aug 2018 - KDIGO Clinical Practice Guideline for Glomerulonephritis PICO (14.3) Population: Patients with focal segmental glomerulosclerosis Intervention: Cyclosporin Comparator: Mycophenolate mofetil plus dexamethasone

Outcome Timeframe


Absolute effect estimates

Certainty in effect estimates (Quality of evidence) Plain text summary Mycophenolat

e mofetil plus dexamethason

e Cyclosporin

All-cause mortality

12 months

Relative risk: 0.18 (CI 95% 0.01 - 3.75)

Based on data from 138 patients in 1 studies

Follow up 19.5 months

30 per 1000

5 per 1000 Low

Due to very serious imprecision1

Cyclosporin compared with MMF plus

dexamethasone may have little or no

difference on all-cause mortality



Relative risk: 2.29 (CI 95% 0.46 - 11.41)



15 per 1000

34 per 1000 Low




difference on end-stage kidney disease


≥50% loss of GFR

Relative risk: 4.58 (CI 95% 0.55 - 38.22)



30 per 1000

137 per 1000 Low




difference on ≥50% loss of GFR


Infection

Relative risk: 1.09 (CI 95% 0.61 - 1.93)



242 per 1000

264 per 1000 Low




difference on infection Difference: 22 more per 1000

(CI 95% 94 fewer - 225 more)

Infection - requiring

hospitalization5

Relative risk: 0.65 (CI 95% 0.22 - 1.96)



106 per 1000

69 per 1000

Low Due to very serious imprecision6



difference on serious infection requiring hospitalizations


Malignancy

(CI 95% - )



Complete remission 12 months

Relative risk: 2.41 (CI 95% 0.87 - 6.71)



91 per 1000

219 per 1000 Low




difference on complete remission


Total hospitalizations

Relative risk: 0.79 (CI 95% 0.39 - 1.57)



212 per 1000

167 per 1000 Low




difference on total hospitalizations



Measured by: Scale: - High better



GFR loss

1. Imprecision: Very Serious. 2. Imprecision: Very Serious. Wide confidence intervals, Only data from one study, Low number of patients; 3. Imprecision: Very Serious. Wide confidence intervals, Low number of patients, Only data from one study; 4. Imprecision: Very Serious. Wide confidence intervals, Only data from one study, Low number of patients; 5. Serious infections requiring hospitalization 6. Imprecision: Very Serious. Wide confidence intervals, Only data from one study, Low number of patients; 7. Imprecision: Very Serious. Only data from one study, Low number of patients, Wide confidence intervals; 8. Imprecision: Very Serious. Wide confidence intervals, Only data from one study, Low number of patients;

21 Aug 2018 - KDIGO Clinical Practice Guideline for Glomerulonephritis PICO (14.4) Population: Patients with focal segmental glomerulosclerosis Intervention: Cyclosporin plus low dose prednisone Comparator: Prednisone

Outcome Timeframe



(Quality of evidence) Plain text summary Prednisone

Cyclosporin plus low dose

prednisone

All-cause mortality

(CI 95% - )




Relative risk: 0.35 (CI 95% 0.13 - 0.98)

Based on data from 49 patients in 1 studies Follow up 50 months

435 per 1000

152 per 1000 Low

Due to serious risk of bias, Due to serious imprecision1

Cyclosporin plus low dose prednisone compared with

prednisione alone may decrease end-stage

kidney disease Difference: 283 fewer per 1000

(CI 95% 378 fewer - 9 fewer)

Infection

(CI 95% - )


Difference: fewer

Malignancy

(CI 95% - )



≥50% loss of GFR

(CI 95% - )



Complete remission

Relative risk: 2.67 (CI 95% 0.11 - 62.42)


0 per 1000

0 per 1000



There were too few who experienced the

complete remission, to determine whether

cyclosporin plus low dose prednisone compared with

prednisione alone made a difference


Partial remission

Relative risk: 7.96 (CI 95% 1.09 - 58.15)


43 per 1000

342 per 1000 Moderate

Due to serious risk of bias, Due to serious imprecision,Upgraded due

to Large magnitude of effect3


prednisione alone probably increase partial remission

Difference: 299 more per 1000 (CI 95% 4 more - 2457 more)

Doubling serum creatinine

Relative risk: 1.18 (CI 95% 0.72 - 1.94)


522 per 1000

616 per 1000 Low



prednisone alone may have little or no

difference on doubling serum creatinine


Annual GFR loss




1. Risk of bias: Serious. Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias; Imprecision: Serious. Only data from one study;

2. Risk of bias: Serious. Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias; Imprecision: Very Serious. Only data from one study, Low number of patients, Wide confidence intervals;

3. Risk of bias: Serious. Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias; Imprecision: Serious. Wide confidence intervals, Only data from one study, Low number of patients; Upgrade: Large magnitude of effect.

4. Risk of bias: Serious. Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias; Imprecision: Serious. Only data from one study, Low number of patients;

21 Aug 2018 - KDIGO Clinical Practice Guideline for Glomerulonephritis PICO (14.5) Population: Patients with focal segmental glomerulosclerosis Intervention: Cyclosporin plus prednisolone Comparator: Methylprednisolone

Outcome Timeframe



(Quality of evidence) Plain text summary Methylprednis

olone Cyclosporin

plus prednisolone

All-cause mortality

(CI 95% - )




(CI 95% - )



≥50% loss of GFR

(CI 95% - )



Infection

(CI 95% - )


Difference: fewer

Malignancy

(CI 95% - )



Complete remission

Relative risk: 2.31 (CI 95% 0.55 - 9.74)


167 per 1000



We are uncertain whether cyclosporin plus prednisolone

compared with methylprednisone

increases or decreases complete remission


Annual GFR loss


Mean

Mean


GFR loss Difference: MD null lower

1. Primary study Bhaumik 2002 Baseline/comparator: Control arm of reference used for intervention . 2. Risk of bias: Serious. Unclear sequence generation/ generation of comparable groups, resulting in potential for selection bias, unclear

concealment of allocation during randomization process, resulting in potential for selection bias, Unclear loss to follow up and selective outcome reporting; Imprecision: Very Serious. Wide confidence intervals, Only data from one study, Low number of patients;

21 Aug 2018 - KDIGO Clinical Practice Guideline for Glomerulonephritis PICO (14.6) Population: Patients with focal segmental glomerulosclerosis Intervention: Cyclosporin plus prednisone Comparator: Chlorambucil plus prednisone

Outcome Timeframe



(Quality of evidence) Plain text summary Chlorambucil plus

prednisone

Cyclosporin plus

prednisone

All-cause mortality

(CI 95% - )




Relative risk: 1.06 (CI 95% 0.33 - 3.35)

Based on data from 58 patients in 1 studies Follow up 4 years

167 per 1000

177 per 1000

Very Low Due to very serious risk of bias, Due to very serious imprecision1

We are uncertain whether cyclosporin

plus prednisone compared with

chlorambucil plus prednisone increases or

decreases end-stage kidney disease


≥50% loss of GFR

(CI 95% - )



Infection

(CI 95% - )


Difference: fewer

Malignancy

(CI 95% - )



Complete remission

Relative risk: 1.41 (CI 95% 0.48 - 4.16)

Based on data from 58 patients in 1 studies2

Follow up 4 years

167 per 1000

235 per 1000

Very Low Due to very serious risk of bias, Due to very serious imprecision3

We are uncertain whether cyclosporin

plus prednisone compared with

chlorambucil plus prednisone increases or

decreases complete remission






1. Risk of bias: Very Serious. Inadequate sequence generation/ generation of comparable groups, resulting in potential for selection bias, Inadequate concealment of allocation during randomization process, resulting in potential for selection bias, Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, Selective outcome reporting; Imprecision: Very Serious. Wide confidence intervals, Only data from one study, Low number of patients;

2. Primary study Heering 2004 Baseline/comparator: Control arm of reference used for intervention . 3. Risk of bias: Very Serious. Inadequate sequence generation/ generation of comparable groups, resulting in potential for selection bias,

Inadequate concealment of allocation during randomization process, resulting in potential for selection bias, Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, Selective outcome reporting; Imprecision: Very Serious. Wide confidence intervals, Only data from one study, Low number of patients;

21 Aug 2018 - KDIGO Clinical Practice Guideline for Glomerulonephritis PICO (14.7) Population: Patients with focal segmental glomerulosclerosis Intervention: Mycophenolate mofetil Comparator: Prednisone

Outcome Timeframe



(Quality of evidence) Plain text summary Prednisone Mycophenolat

e mofetil

All-cause mortality

(CI 95% - )




(CI 95% - )



≥50% loss of GFR

(CI 95% - )



Infection

Relative risk: 0.75 (CI 95% 0.14 - 3.94)

Based on data from 36 patients in 1 studies Follow up Mean 16.3

months

158 per 1000



We are uncertain whether mycophenolate mofetil compared with

prednisone increases or decreases infection


Malignancy

(CI 95% - )



Complete remission

Relative risk: 1.05 (CI 95% 0.58 - 1.88)

Based on data from 33 patients in 1 studies Follow up Mean 16.3

months

563 per 1000

591 per 1000 Low


Mycophenolate mofetil compared with

prednisone may have little or no difference on

complete remission Difference: 28 more per 1000

(CI 95% 236 fewer - 495 more)





GFR

Measured by: mL/min Scale: - High better

Based on data from 33 patients in 1 studies3 Follow up Mean 16.3

months

Mean

Mean Very Low


We are uncertain whether mycophenolate mofetil compared with

prednisone increases or decreases GFR

Difference: 4 higher (CI 95% 5.32 lower - 13.32 higher)


2. Risk of bias: Serious. Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias; Imprecision: Serious. Only data from one study, Low number of patients;

3. Primary study Senthil Nayagam 2008 Baseline/comparator: Control arm of reference used for intervention .

21 Aug 2018 - KDIGO Clinical Practice Guideline for Glomerulonephritis PICO (14.8) Population: Patients with focal segmental glomerulosclerosis Intervention: Dexamethasone 2 weekly Comparator: Dexamethasone 4 weekly

Outcome Timeframe



(Quality of evidence) Plain text summary Dexamethason

e 4 weekly Dexamethason

e 2 weekly

All-cause mortality

(CI 95% - )




(CI 95% - )



≥50% loss of GFR

(CI 95% - )



Infection

(CI 95% - )


Difference: fewer

Malignancy

(CI 95% - )


Difference: fewer

Complete remission

(CI 95% - )

No studies were found that looked at complete

remission Difference: fewer

Partial remission

Relative risk: 0.75 (CI 95% 0.07 - 7.73)


334 per 1000



We are uncertain whether

dexamethasone 2 weekly compared to 4 weekly increases or

decreases partial remission






GFR

Measured by: mL/min Scale: - High better

mL/minMean

mL/minMean


We are uncertain whether


Difference: 13 lower (CI 95% 40.53 lower - 14.53 higher)

very serious imprecision3 dexamethasone 2 weekly compared to 4 weekly increases or

decreases GFR 1. Risk of bias: Serious. Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias; Imprecision: Very

Serious. Wide confidence intervals, Only data from one study, Low number of patients; 2. Primary study Cho 2011 Baseline/comparator: Control arm of reference used for intervention . 3. Risk of bias: Serious. Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias; Imprecision: Very

Serious. Wide confidence intervals, Only data from one study, Low number of patients;

21 Aug 2018 - KDIGO Clinical Practice Guideline for Glomerulonephritis PICO (14.9) Population: Patients with focal segmental glomerulosclerosis Intervention: Fresolimumab Comparator: Placebo

Outcome Timeframe



(Quality of evidence) Plain text summary Placebo Fresolimumab

All-cause mortality

(CI 95% - )




(CI 95% - )



≥50% loss of GFR

(CI 95% - )



Infection

(CI 95% - )


Difference: fewer

Malignancy

(CI 95% - )



Complete remission

(CI 95% - )



Partial remission - Fresolimumab 1

mg 4 months

Relative risk: 3.67 (CI 95% 0.19 - 69.01)


0 per 1000

0 per 1000 Very Low


There were too few who experienced the partial remission, to determine whether fresolimumab (1 mg) compared to

placebo made a difference


Partial remission - Fresolimumab 4

mg 4 months

Relative risk (CI 95% - )


0 per 1000

per 1000

There were too few who experienced the partial remission, to determine whether fresolimumab

(4mg) compared to placebo made a

difference

Difference: fewer per 1000

Annual GFR loss




GFR loss

1. Primary study Vincenti 2017 Baseline/comparator: Control arm of reference used for intervention . 2. Risk of bias: Serious. Unclear sequence generation/ generation of comparable groups, resulting in potential for selection bias, Unclear

concealment of allocation during randomization process, resulting in potential for selection bias; Imprecision: Very Serious. Wide confidence intervals, Only data from one study, Low number of patients;

3. Primary study Vincenti 2017 Baseline/comparator: Control arm of reference used for intervention .

21 Aug 2018 - KDIGO Clinical Practice Guideline for Glomerulonephritis PICO (14.10) Population: Patients with focal segmental glomerulosclerosis Intervention: Adalimumab Comparator: Galactose or conservative therapy

Outcome Timeframe



(Quality of evidence) Plain text summary Galactose or conservative

therapy Adalimumab

All-cause mortality



0 per 1000

0 per 1000



There were too few who experienced all-cause mortality, to determine whether adalimumab compared to control

(conservative therapy or galactose) made a

difference



Relative risk: 2.0 (CI 95% 0.15 - 27.45)


71 per 1000



We are uncertain whether adalimumab

increases or decreases end-stage kidney

disease Difference: 71 more per 1000

(CI 95% 60 fewer - 1878 more)

≥50% loss of GFR

(CI 95% - )



Infection

Relative risk: 1.11 (CI 95% 0.6 - 2.04)


643 per 1000




increases or decreases infection Difference: 71 more per 1000

(CI 95% 257 fewer - 669 more)

Serious adverse event -

hospitalization

Relative risk: 3.0 (CI 95% 0.64 - 14.02)


143 per 1000




increases or decreases serious adverse event -

hospitalization Difference: 286 more per 1000

(CI 95% 51 fewer - 1862 more)

50% reduction in proteinuria

Relative risk: 0.17 (CI 95% 0.01 - 2.71)


357 per 1000




increases or decreases 50% reduction in

proteinuria Difference: 296 fewer per 1000

(CI 95% 353 fewer - 610 more)

Malignancy



per 1000

per 1000



There were too few who experienced

malignancy, to determine whether

adalimumab compared to control (conservative therapy or galactose)

made a difference

Difference: fewer per 1000

Complete remission

(CI 95% - )






1. Systematic review [19] with included studies: FONT II 2011 Baseline/comparator: Control arm of reference used for intervention . 2. Risk of bias: Serious. Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, Unclear sequence

generation/ generation of comparable groups, resulting in potential for selection bias, Unclear concealment of allocation during randomization process, resulting in potential for selection bias; Imprecision: Serious. Only data from one study, Low number of patients, Wide confidence intervals, Only data from one study, Low number of patients;


generation/ generation of comparable groups, resulting in potential for selection bias, Unclear concealment of allocation during randomization process, resulting in potential for selection bias; Imprecision: Very Serious. Wide confidence intervals, Only data from one study, Low number of patients;







11. Risk of bias: Serious. Inadequate/lack of blinding of participants and personnel, resulting in potential for performance bias, Unclear sequence generation/ generation of comparable groups, resulting in potential for selection bias, Unclear concealment of allocation during randomization process, resulting in potential for selection bias; Imprecision: Serious. Only data from one study, Low number of patients;

References [19] Immunosuppressive treatment for focal segmental glomerulosclerosis in adults. 2018;

kdigo gn guideline update – evidence summary …...1 kdigo gn guideline update – evidence...

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